Translational Sports Medicine

Translational Sports Medicine covers the principles of evidence-based medicine and applies these principles to the design of translational investigations. This title is an indispensable tool in grant writing and funding efforts with its practical, straightforward approach that will help aspiring investigators navigate challenging considerations in study design and implementation. It provides valuable discussions of the critical appraisal of published studies in translational sports medicine, allowing the reader to learn how to evaluate the quality of such studies with respect to measuring outcomes and to make effective use of all types of evidence in patient care.

In short, this practical guidebook will be of interest to every medical researcher or sports medicine clinician who has ever had a good clinical idea but not the knowledge of how to test it. Readers will come to fully understand important concepts, including case-control study, prospective cohort study, randomized trial and reliability study. Medical researchers will benefit from greater confidence in their ability to initiate and execute their own investigations, avoid common pitfalls in translational sports medicine, and know what is needed in collaboration.

• Focuses on the principles of evidence-based medicine and applies these principles to translational investigations within sports medicine
• Details discussions of the critical appraisal of published studies in translational sports medicine, supporting evaluation with respect to measuring outcomes and making effective use of all types of evidence in patient care
• Written by experts in the sports medicine field

• Language: English
• Publisher: Academic Press
• Release date: Aug 14, 2023
• ISBN: 9780323913348

Book preview

Translational Sports Medicine

Edited by

Adam E.M. Eltorai

Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, United States

Jeffrey A. Bakal

University of Alberta, Faculty of Medicine and Dentistry, Edmonton Alberta, Canada

Steven F. DeFroda

University of Missouri Department, Orthopaedic Surgery, Columbia, MO, United States

Brett D. Owens

Department of Orthopaedic Surgery, The Warren Alpert Medical School of Brown University, Providence, RI, United States

Table of Contents

Cover image

Title page

Handbook for Designing and Conducting Clinical and Translational Research

Copyright

List of contributors

Preface

Part I. Introduction

Part I Introduction

Chapter 1. Introduction

Chapter 2. The translational process

Key points

Why it matters

Translational research

Get started

Pitfalls to avoid

Real-world examples

Chapter 3. Scientific method

Key points

Why it matters?

Making an observation

Formulating a question

Generating a hypothesis

Making predictions

Experimentation and data gathering

Analysis and drawing conclusions

Summary

Get started

Potential pitfalls

Example case

Chapter 4. Basic research

Key points

Why it matters?

Reductionist approach

Reductionist versus applied research

Objectives

Disciplines

Common lab methods/techniques

Major areas of current investigation

Get started

Pitfalls to avoid

Real-world examples

Part II. Pre-clinical

Part II Pre-clinical

Chapter 5. Overview of preclinical research

Key points

Why it matters

Get started

The process for preclinical research

Common research techniques for preclinical research

Types of common experimentation methods in preclinical research

Common areas of preclinical sports medicine research

Growth factor study and mechanisms of delivery

Cell-based interventions

Biomechanical testing of proposed surgical procedures using cadaver specimens

Computer modeling for kinematics and implant design

Potential pitfalls to avoid

Translatability

Controls

Reproducibility

Chapter 6. What problem are you solving?

Key points

Defining the problem

Solving the problem

Framing the problem for research

Get started

Pitfalls

Examples

Chapter 7. Types of interventions: drugs, devices, diagnostic, procedural technique, and behavior change

Drugs

Devices

Diagnostic

Procedural technique

Behavior change

Chapter 8. Beyond drugs and surgery: a look at orthobiologics

Key points

Cell therapies

Blood-derived products

Recombinant growth factors

Gene therapies

Small molecules

Fibrosis

Exosomes

Challenges associated with defining the orthobiologics' efficacy

Chapter 9. Drug testing

Key points

Safety and toxicity testing

Good Laboratory Practice

Areas of current investigation

Potential pitfalls

Real-world examples

Get started

Funding considerations

Chapter 10. Device discovery and prototyping

Introduction

Innovation in orthopedics

Needs and market capacity assessments

Prototyping

Cost and budgetary considerations

Conclusion

Chapter 11. Device testing

Key points

Potential pitfalls

Chapter 12. Diagnostic discovery

Introduction

Areas of current investigation

Potential pitfalls to avoid

Get started

Real-world example

Resources and funding sources

Chapter 13. Diagnostic testing

Key points

Introduction

Learning and defining terms

Goals: what does a good diagnostic test look like?

Real-world examples

Regulatory considerations

Get started

Potential pitfalls

Chapter 14. Preclinical: discussion of FDA product categories (what the FDA covers, regulated or not)

Key points

Introduction

Human foods and supplements

Human drugs

Biologics

Medical devices

Radiation producing devices

Cosmetics

Veterinary products

Tobacco products

Resources: additional reading, consultants, contractors

Get started

Potential pitfalls

Real-world examples

Chapter 15. Procedural technique development

Key points

Body of text

Phases of development for surgical techniques

Conclusion

Real-world examples from the published literature to further illustrate the concept and to serve as references or additional resources

Get started section

Pitfalls to avoid

Chapter 16. Behavioral intervention studies

Key points

Introduction

Stage model for behavioral intervention studies

Recently published representative studies

Get started

Pitfalls to avoid

Chapter 17. Artificial intelligence

Key points

Introduction

Designing a clinical research study using AI

Steps to designing an AI-based clinical research study

Examples of artificial intelligence in clinical research

Get started

Potential pitfalls

Resources

Part III. Clinical: Fundamentals

Part III Clinical: Fundamentals

Chapter 18. Introduction to clinical research: what is it? why is it needed?

Key points

Get started

Real-world examples

Chapter 19. The question: types of research questions and how to develop them

Key points

Why it matters?

Types of clinical research questions

Development of a clinical research question

Get started

Potential pitfalls

Chapter 20. Study population: who and why them?

Key points

Why this matters

Selecting sampling methods by study needs

Types of sampling

Get started

Potential pitfalls

Chapter 21. Outcome measurements: what data is being collected and why?

Key points

Why this matters

What are outcome measures?

Selecting outcome measures

Patient-reported outcome measures

Clinical versus statistical significance

Get started

Potential pitfalls

Chapter 22. Optimizing the question: balancing significance and feasibility

Key points

Why it matters

Real world examples

Get started

Potential pitfalls to avoid

Resources/further reading

Part IV. Statistical principles

Part IV Statistical principles

Chapter 23. Common issues in analysis

Key points

Introductory section/why it matters

Limitations by study design

Observational studies

Statistical significance and the P-value: common misunderstood concepts in analysis

Conclusions

Get started

Potential pitfalls

Examples of …

Resources

Chapter 24. Basic statistical principles

Sensitivity

Specificity

Positive predictive value

Negative predictive value

Risk quantification

Incidence

Prevalence

Precision

Accuracy

Statistical distribution

Chapter 25. Distribution

Key points

Introduction

Discrete distribution

Continuous distribution

Potential pitfalls to avoid

Chapter 26. Research hypothesis and error types

Hypothesis

Errors

Chapter 27. Power

Key points

Why it matters?

Power

Pitfalls to avoid

Chapter 28. Multivariable regression models

Key points

Why it matters

Types of regression

Get started

Chapter 29. How to choose appropriate bivariate test

Key points

Introductory section/why it matters

Get started

Potential pitfalls

Examples

Single sample t-test

Paired t-test

Independent group t-test

Independent sample t-test assuming unequal variances

Wilcoxon–Mann–Whitney test

Chapter 30. Categorical variable analyses: chi-square, Fisher exact, Mantel–Haenszel

Key points

Introduction

Chi-square

The Fisher's exact test

Mantel–Haenszel

Pitfalls to avoid

Chapter 31. Analysis of variance: ANOVA

Key points

Introduction

One-way ANOVA

Conclusions

Get started

Chapter 32. Correlation

Introduction

Key aspects

Chapter 33. Statistical bias

Chapter 34. Basic science statistics

Chapter 35. Sample size

Chapter 36. Statistical software

Key points

Excel

SPSS

SAS

STATA

R

Potential pitfalls to avoid

Get started

Part V. Clinical: Study types

Part V Clinical: Study types

Chapter 37. Design principles: hierarchy of study types

Key points

Why it matters

Body of text

Get started

Potential pitfalls to avoid

Real-world examples

Chapter 38. Case series: design, measures, and an example

Why it matters

Definition of a case series

Benefits and limitations to investigator

Step-by-step design

Examples of case series

Budgetary considerations

Get started

Potential pitfalls

Chapter 39. Case-control study

Key points

Introduction

Benefits and limitations

Budgetary considerations

Standard research personnel and roles

Study design and getting started

Pitfalls to avoid

Get started

Examples from current literature

Chapter 40. Cohort studies

Key points

Introduction

Design

Potential pitfalls to avoid

Research team personnel

Budgetary considerations

Get started

Chapter 41. Cross-section study

Key points

Introduction

Benefits and limitations

Budgetary considerations

Standard research personnel and roles

Study design and getting started

Get started

Pitfalls to avoid

Examples from current literature

Chapter 42. Longitudinal study: design, measures, classic example

Key points

Get started

Real-world example

The research team

Budgetary considerations

Potential pitfalls to avoid

Resources additional reading

Chapter 43. Meta-analysis

Key points

Introduction

Design

Strengths and limitations

Potential pitfalls to avoid

Research team personnel

Budgetary considerations

Get started

Chapter 44. Cost-effectiveness study: design, measures, classic example

Key points

Why it Matters?

Introduction

Study design

Examples

Research personnel and budgetary considerations

Potential pitfalls to avoid

Get started

Resources

Chapter 45. Diagnostic test evaluation: design, measures, classic example

Key points:

Getting started: Diagnostic test parameters

Designing studies to avoid common biases

Use of standards in antigen testing for COVID-19

Potential pitfalls

Resources

Chapter 46. Reliability study: design, measures, classic example

Key points

What is reliability?

How do we measure reliability?

Study design

Examples

Budgetary considerations

Pitfalls to avoid

Get started

Chapter 47. Database types and basic data management design principles for healthcare research

Key Points

Get started

Potential pitfalls

Resources

Chapter 48. Survey studies and questionnaires

Key points

Why it matters?

Designing a survey study

Research team personnel and roles

Benefits and limitations

Budget and funding

Real-world application

Potential pitfalls

Get started

Chapter 49. Qualitative methods and mixed methods

Key points

Why it matters?

Qualitative research

Mixed methods research

Designing a study

Other considerations

Real-world examples

Get started

Common pitfalls

Resources

Part VI. Clinical: Trials

Part VI Clinical: Trials

Chapter 50. Randomized controlled trials

Key points

Why it matters?

Choosing a research question

Randomization

Unit of randomization

Experimental design

Control group

Blinding

Outcome measures

Generalizability

Attrition

Ethical concerns

Get started

Potential pitfalls

Chapter 51. Nonrandomized controlled trials

Introduction

Define your intervention

Define the study population

Define the study outcomes

Allocation of subjects

Study examples

Potential pitfalls

Starting your study

Chapter 52. Historical control: design, measures, classic example

Key points

Chapter 53. Crossover studies

Key points

Introduction

Overview crossover designs

Analysis of simple crossover designs

Advantages

Limitations

Ethics

Crossover design for dosing trials

Study design examples

Potential pitfalls

Get started

Chapter 54. Withdrawal studies: design, measures, classic example

Key points

Introduction

Benefits

Limitations

Standard research team personnel and roles

Budgetary considerations and how to fund

Chapter 55. Factorial design: design, measures, classic example

Key points

Get started

Potential pitfalls to avoid

What is a factorial design study?

How is a factorial design study's data interpreted?

Factorial design versus randomized control trial

Real-world examples of factorial design application in translational sports medicine

Chapter 56. Group or cluster controlled trials: design, measures, classic example

Key points

Why it matters?

Group/cluster-allocated trials

Case number calculation

Get started

Potential pitfalls

Real-world examples

Chapter 57. Hybrid design: design, measures, classic examples

Key Points

Introduction

Get started (see Table 57.3)

Benefits of HD

Potential pitfalls

Budgetary considerations

Chapter 58. Large, pragmatic clinical trials

Key points

Benefits

Limitations

Steps to designing a pragmatic trial

Standard research team and roles

Budgetary considerations

Get started

Potential pitfalls

Chapter 59. Equivalence and noninferiority: design, measures, classic example

Key points

Why it matters

Real life example #1

Real life example #2

Real life example #3

Potential pitfalls

Get started

Chapter 60. Translational sports medicine: handbook for designing and conducting clinical and translational research

Key points

Introduction

Advantages

Disadvantages

Principles of designing an adaptive design clinical trial

Practical considerations

Potential pitfalls

Get started

Chapter 61. Randomization: fixed or adaptive procedures

Key points

Get started

Potential pitfalls to avoid

Chapter 62. Blinding: who, when and how? importance and impact on findings

Key points

Single blinding

Double blinding

Triple blinding

Conclusion

Get started

Potential pitfalls to avoid

Chapter 63. Multicenter considerations

Key points

Introduction

Benefits and challenges

How to design a multicenter study

Chapter 64. Phase 0 trials: window of opportunity

Key points

Introductory section/Why it matters?

Study design and practical considerations

Benefits and challenges

Standard research team and roles

Budgetary considerations and funding this stage

Conclusion

Get started

Potential pitfalls

Chapter 65. Registries

Key points

Introduction

Divisions of database research

Clinical registries

US databases utilized in arthroplasty research

Functional comparison of available registries and databases

Sample sizes of lower extremity arthroplasty procedures in databases

Journals publishing database/registry research

Conclusion

Chapter 66. Phases of clinical trails

Key points

Avoiding pitfalls

Chapter 67. IDEAL framework: framework for describing the stages of innovation in surgery

Key points

Introduction

Stage 1: Innovation

Stage 2a: Development

Stage 2b: Exploration

Stage 3: Assessment

Stage 4: Long-term study

Conclusions

Get started

Potential pitfalls to avoid

Real-world examples

Part VII. Clinical preparation

Part VII Clinical preparation

Chapter 68. Patient perspectives

Key points

Why it matters?

Regulatory guidance on incorporating patient perspectives

Building a study team to consider patient perspectives

Considering patient perspective during research design

Benefits of considering patient perspective during research design

The informed patient

Considering the patient during dissemination of findings

Conclusions

Get started

Potential pitfalls

Resources: additional reading, consultants, contractors

Chapter 69. Budgeting

Introduction

Types of funding

Considerations for budgeting

Timelines for study funding

Conclusion

Chapter 70. Ethics and review boards

Key points

Why ethics in research matters

Guiding principles

Part A: Boundaries between practice and research

Part B: Basic ethical principles

Part C: Applications

Getting started with human subject research

Common pitfalls

Resources

Chapter 71. Regulatory considerations for sports medicine technologies: new drugs and medical devices

Key points

Regulatory pathways

FDA requirements

Data collection considerations for nonapproved technologies

Issues with regulatory agencies for clinical studies

Get started

Potential pitfalls

Real-world examples

Resources

Chapter 72. Funding approaches

Sources of funding

Grant writing

Conclusion

Chapter 73. Conflicts of interest

Key points

Get started

Why it matters

Body of text

Potential pitfalls to avoid

Real-world examples from published literature

Chapter 74. Subject recruitment

Key points

Clinical research scenario

Developing and implementing a recruitment strategy

Ethical considerations in patient recruitment

Get started

Potential pitfalls

Resources: additional reading, consultants, contractors

Chapter 75. Data management: how to manage data safely and effectively in an organized manner

Key points

Introduction

Data management considerations

Data organization

Resources

Compliance/data management plan

Data retention

Real-world example

Get started

Potential pitfalls to avoid

Chapter 76. A practical guide to conducting research in the acute setting

Key points

Introduction

Benefits and challenges for engaging in research for sports medicine clinicians

General guidelines for designing a research study in a medical setting

Distilling clinical observations into research questions and hypotheses

Planning the research

Creating a research team with clinical expertise and awareness

Positioning clinical research activity for funding

Potential pitfalls

Get started

Conclusion

Chapter 77. Special populations

Key points

Introduction

Where are we today?

The ideal research team

Principles of the effective research team

Orthopedic sports medicine research

Nonphysician personnel

Tactics to attract minorities

Potential pitfalls

Get started

Real-world examples

Chapter 78. Subject adherence

Introduction

Intention to treat

Per protocol and as treated

Stylized example

Per protocol

As treated

Clinical example

What have we learned?

Pitfalls

Get started

Resources

Chapter 79. Time-to-event outcomes and survival analysis

Key points

Why it matters

A few foundational concepts

Get started

Potential pitfalls

Examples

Resources

Chapter 80. Monitoring committee in clinical trials

Key points

Why it matters

Get started

Potential pitfalls

Examples

Resources

Part VIII. Regulatory basics

Part VIII Regulatory basics

Chapter 81. FDA overview

Key points

Why it matters

The FDA

Mission

Structure, organization, and hierarchy

What does the FDA regulate?

Foods

Drugs

Biologics

Medical devices

Electronic products that give off radiation

Cosmetics

Veterinary products

Tobacco products

Center for drug evaluation and research

Structure

Definition of a drug

Prescription drugs

Over-the-counter drugs

Biological therapeutics

Drug development and review

Center for devices and radiological health

Structure

What is a medical device?

What to avoid

Chapter 82. Investigational new drug (IND) application

Key points

What is an IND and why is it important?

What are the different types of IND?

When is an IND required?

When is it not necessary to have an IND?

What does an IND consist of?

Form 1571

Form FDA-1572

Additional information

Protocol and information amendments

Safety reports (FDA form 3500A)

Annual reports

Clinical holds, termination, and inactivation

Conclusions

Get started

Real-world examples

Potential pitfalls

Additional resources

Chapter 83. New drug application

Introduction

Get started

Chapter 84. Medical devices

Key points

Overview

Medical devices classification

Pathways

Funding

Common challenges

Chapter 85. Radiation-emitting electronic products

Key points

Why does it matter?

Overview

Components, processes, and pathways

Common challenges and real-world examples

Chapter 86. Orphan drugs

Overview

Process/pathways

Components

Common examples

Budgetary considerations

Chapter 87. Biological drugs

Real-world examples

Key points and potential pitfalls to avoid

Chapter 88. Combination products

Key points

Get started

Potential pitfalls

Chapter 89. Cosmetics in sports medicine

Process/Pathways1

Components

Examples

Common challenges3

Budgetary consideration and how to fund

Chapter 90. CMC and GxP: chemistry, manufacturing, and controls & good practice' guidelines and regulations

Key points

Chemistry, manufacturing, and controls

Good practice' guidelines and regulations

Chapter 91. Non-US regulatory

Key points

Introductory section/Why it matters?

Regulation outside the United States

Chapter 92. Postmarket drug safety monitoring

Chapter 93. Postmarket device safety monitoring

Key points

Introduction

Interim Postmarket Surveillance Report

Final Postmarket Surveillance Report

Evaluation of Postmarket Surveillance Final Report

Failure to comply with postmarket surveillance

Public disclosure of postmarket surveillance plan

Potential pitfall

Get started

Part IX. Clinical implementation

Part IX Clinical implementation

Chapter 94. Implementation research

Key points

Get started

Chapter 95. Design and analysis

Introduction

Overview of implementation objectives and outcomes

Intervention research methods example #1: RE-AIM framework for planning and evaluating outcomes

Intervention research methods example #2: mixed methods

Methodological challenges in implementation research

Study design

Experimental—waitlist randomized controlled trial

Quasi-experimental—multiple baseline trial

Observational study design

Conclusion

Get started

Potential pitfalls

Real-world examples

Resources

Chapter 96. Mixed methods in concussion research

Summary

Why it matters

Defining mixed methods

Types of mixed methods designs

Examples in concussion research

Get started

Pitfalls to avoid

Resources

Chapter 97. Implementation of multimodal concussion research within military medical environments

Key points

Introduction

Resources

Translation example 1. Initial prototype of the Bethesda Eye and Attention Measure

Translational example 2. Initial demonstration of sensitivity in the mTBI clinical population

Translational example 3. Testing an advanced prototype in the military clinical environment

Disclaimer

Chapter 98. Guideline development

Key points

Introduction/why it matters

Get started

Part X. Public health

Part X Public health

Chapter 99. Public health

Key points

Why it matters

Get started

Examples

Resources

Chapter 100. Epidemiology of sports injuries

Key points

Introduction

Sports injuries in adolescents

Demographic data on sports injuries in the United States

International sports injury data

Population level effects of sports injuries

Chapter 101. Factors

Key points

Multifactorial considerations in public health

Get started

Potential pitfalls

Resources

Chapter 102. Good questions—asking the right public health questions

Key points

Why it matters

Examples

Potential pitfalls to avoid

Get started

Chapter 103. Population- and environmental-specific considerations

Key points

Why it matters

Population considerations

Environmental considerations

Potential pitfalls to avoid

Get started

Chapter 104. Law, policy, and ethics

Key points

Why it matters

Overview

Objectives of public health law, policy, and ethics in translational research

Methods

Impact

Challenges

Get started

Potential pitfalls

Chapter 105. Healthcare institutions and systems

Key points

Using translational research to impact policy

Types of healthcare institutions

Interactions between healthcare institutions

Get started

Potential pitfalls

Examples of the influence of healthcare institutions on the translational research process

Resources

Chapter 106. Public health institutions and systems

Key points

Key public health institutions

States and local departments of health

Nongovernmental public health entities

Partnership between translational researchers and public health entities

Social determinants of health

Get started

Potential pitfalls

CMS—Comprehensive Care for Joint Replacement

PCORI

Social determinants of health

Resources

Part XI. Practical resources

Part XI Practical resources

Chapter 107. Presenting data

Chapter 108. Manuscript preparation

Key points

Preface

Abstract

Introduction

Materials and methods

Results

Discussion

Conclusion

References

Get started

Pearls and pitfalls—suggested by Provenzale2

Real-world examples

Resources

Chapter 109. Promoting research

Key points

Introduction

Methods to promote research

Real-world example on how to rewrite abstract components to be more direct and succinct

Real-world example of an effective table that succinctly delivers data

Real-world example of how to create an abstract that is tweetable and easily shared

Author impact metrics

Academic advancement

Risks

Get started

Pitfalls to avoid

Resources

Chapter 110. Quality improvement

Key points

Why it matters?

Introduction

Reporting and disseminating results

Example studies

Personnel

Funding

Potential pitfalls to avoid

Get started

Additional resources

Chapter 111. Team science and building a team

Key points

Why it matters

What is team science?

Why team science?

Examples of team science

Is team science right for you?

Building a team

Finding collaborators

Get started

Potential pitfalls to avoid

Additional reading

Chapter 112. Types of intellectual property

Four main types

Recommendations for timing of filing

Example patent template21,22

Budgetary considerations

Chapter 113. Venture pathways

Key points

Main text

Basics of starting a company

Licensing

Venture capital funding

Exit strategies

Get started

Potential pitfalls to avoid

Real-world examples

Resources

Chapter 114. Utilizing National Institutes of Health (NIH) grants to fund translational research: An Overview

Key points

Introduction to the National Institutes of Health grant application process

Initial preparation for the application process and important personnel

Application completion and review process

Award processing

Pitfalls to avoid

Get started

Real world examples

Additional resources

Chapter 115. Sample forms and templates

Key points

IRB protocols

IRB budgets

Grant proposals

Consort diagram

Equator guidelines

Lincoln and guba framework

Real-world examples

Potential pitfalls to avoid

Glossary

Index

Handbook for Designing and Conducting Clinical and Translational Research

Series Editor

Adam E. M. Eltorai, MD, PhD

Copyright

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Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

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List of contributors

Joseph Abboud,     Rothman Orthopedic Institute, Orthopedic Surgeon, Philadelphia, PA, United States

Kyrillos M. Akhnoukh,     Department of Orthopedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

Alexander Alexandrov,     The Warren Alpert Medical School of Brown University, Providence, RI, United States

Anas Aljabi,     The University of Alabama at Birmingham, Department of Orthopaedic Surgery, Birmingham, AL, United States

Giuliana Colombari Arce,     Universidad de Ciencias Medicas, Costa Rica

Daniel Arias,     Universidad de Ciencias Médicas (UCIMED), Costa Rica

Camilo Andres Avendaño Capriles,     Department of Medicine, Universidad del Norte, Barranquilla, Atlántico, Colombia

Ali Azarpey,     Department of Orthopedic Surgery, Emory University, Atlanta, GA, United States

Vu N. Bach,     The University of Toledo Medical Center, Toledo, OH, United States

Catalina Baez,     Division of Arthroplasty and Joint Reconstruction, Department of Orthopedics and Sports Medicine, University of Florida College of Medicine, Gainesville, FL, United States

Alissa Belzie

Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Matthew J. Best,     Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Julia Beyer,     The University of Toledo Medical Center, Toledo, OH, United States

Meghan E. Bishop,     Department of Orthopaedic Surgery, Division of Sports Medicine, Rothman Orthopaedic Institute, New York, NY, United States

Paulina Bogdan

Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Trevor Bouck,     The University of Toledo Medical Center, Toledo, OH, United States

Brandon Boyd,     Department of Orthopaedics, University of Alabama at Birmingham Hospital, Birmingham, AL, United States

Bryanna Brown,     Department of Health, Human Performance and Recreation/Office for Sport Concussion Research, University of Arkansas, Fayetteville, AR, United States

Michael P. Campbell,     Rothman Orthopaedic Institute, Division of Sports Medicine, Philadelphia, PA, United States

Salvatore Capotosto,     Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, United States

Luis Felipe Cardiel Castro,     Oxford School of Public Health, Oxford University, Oxford, United Kingdom

Noel Bien Tan Carlos,     University of Pittsburgh School of Medicine, Pittsburgh, PA, United States

Felipe Carrasco,     Orthopedics and Traumatology, Universidad de Antioquia, Medellin, CO, Colombia

Juan Cedeno-Serna,     Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States

Jaewon Chang,     William Beaumont Hospital, Department of Orthopaedic Surgery, Sports Medicine Division, Royal Oak, MI, United States

Edward S. Chang,     Inova Orthopaedic and Sports Medicine Group, Fairfax, VA, United States; Washington Nationals, Inova Sports Medicine, Department of Medical Education, University of Virginia School of Medicine, Uniformed Services University of the Health Sciences Fairfax, VA, United States

Christine Chen,     College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Philip Clark,     Department of Orthopaedic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

Geoffrey Cloud,     College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Laura Coco,     School of Speech, Language, and Hearing Sciences, San Diego State University, San Diego, CA, United States

Brian H. Cohen,     Orthopedics Rhode Island, Sports Division, Warwick, RI, United States

Charles Conway,     Department of Orthopedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

Carolina Campuzano Cortina,     Instituto Colombiano del Dolor (Incodol), Medellín, Colombia

Ryan M. Cox,     Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA, United States

Katherine Coyner,     Department of Orthopaedic Surgery, University of Connecticut School of Medicine, Farmington, CT, United States

Cameron Crasto,     The University of Toledo Medical Center, Toledo, OH, United States

Ines Yaritza Cury Perea,     Universidad de Manizales, Caldas, Colombia

Andrew Del Re

The Warren Alpert Medical School of Brown University, Providence, RI, United States

The Mount Sinai Hospital, New York, NY, United States

Nicholas N. DePhillipo

Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States

Mechano-Therapeutics LLC, Philadelphia, PA, United States

Keith Brett Diamond,     Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

Michael B. DiCosmo,     Department of Orthopaedic Surgery, University of Connecticut School of Medicine, Farmington, CT, United States

Meehir Dixit,     Brown University School of Public Health, Providence, RI, United States

Christina M. Dollar,     Inova Health System Sports Medicine Concussion Clinic, Musculoskeletal Service Line, Fairfax, VA, United States

Luke Donovan,     Department of Applied Physiology, Health, and Clinical Sciences, University of North Carolina at Charlotte, Charlotte, NC, United States

Tyler C. Duffield,     Oregon Health & Science University, Portland, OR, United States

Osama Elattar,     The University of Toledo Medical Center, Toledo, OH, United States

R.J. Elbin,     Department of Health, Human Performance and Recreation/Office for Sport Concussion Research, University of Arkansas, Fayetteville, AR, United States

Joseph Elphingstone,     Department of Family Medicine, Phoebe Putney Memorial Hospital, Albany, GE, United States

Ahmed Emara,     Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, OH, United States

Orry Erez,     Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

María Fernanda Escobar

Facultad de Ciencias de la Salud, Universidad Icesi, Cali, Colombia

Ginecology and Obstetrics, Telemedicine Department, Fundación Valle Del Lili, Cali, Colombia

Mark L. Ettenhofer

General Dynamics Information Technology, Falls Church, VA, United States

Traumatic Brain Injury Center of Excellence, Silver Spring, MD, United States

Naval Medical Center San Diego, San Diego, CA, United States

University of California, San Diego, CA, United States

Nathan P. Fackler,     University of California San Diego, Department of Orthopaedic Surgery, San Diego, CA, United States

Ryan T. Fallon,     Department of Orthopaedic Surgery, The Warren Alpert Medical School of Brown University, Providence, RI, United States

Aly M. Fayed,     Department of Orthopaedics and Rehabilitation, University of Iowa Health Care, Iowa City, IA, United States

Mason Ferlic

Exercise and Sport Science Initiative, University of Michigan, Ann Arbor, MI, United States

Department of Statistics, University of Michigan, Ann Arbor, MI, United States

María A. Fernández-Cásseres,     Universidad del Norte, Barranquilla, Colombia

Andrzej Fertala,     Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States

Jorge H. Figueras,     Department of Orthopaedic Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States

Kevin B. Freedman,     Rothman Orthopaedic Institute, Division of Sports Medicine, Philadelphia, PA, United States

Frederick J. Gallun,     Oregon Hearing Research Center, Oregon Health and Science University, Portland, OR, United States

John Paul Garcia,     Division of Plastic Surgery, Mayo Clinic, Jacksonville, FL, United States

Elizabeth E. Ginalis,     Department of Neurological Surgery, Rutgers New Jersey Medical School, Newark, NJ, United States

Brian M. Grawe,     Department of Orthopaedic Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States

Lauren Gruffi,     College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Joseph Guettler,     William Beaumont Hospital, Department of Orthopaedic Surgery, Sports Medicine Division, Royal Oak, MI, United States

Laura Harrison,     Resident Physician, Internal Medicine and Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States

Joe Hart,     Department of Orthopaedic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

Davis A. Hartnett

Internal Medicine Resident at Brigham and Women's Hospital, Boston, MA, United States

Department of Orthopaedic Surgery, Brown University, Warren Alpert School of Medicine, Providence, Rhode Island, United States; Resident Physician, Internal Medicine, Brigham and Women's Hospital, Boston, MA, United States; Brigham and Women's Hospital, Department of Medicine, Boston, MA, United States

Maria F. Henriquez Abramuk,     Barranquilla, Colombia

Mario Hevesi,     Midwest Orthopaedics at Rush, Chicago, IL, United States

Jessalyn K. Holodinsky,     Department of Clinical Neurosciences and the Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

Andrew Horn,     Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

Zainab Ibrahim,     Department of Orthopaedic Surgery, Brown University, Providence, RI, United States

Adem Idrizi

Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

College of Medicine, State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, NY, United States

Gian Christian T. Ignacio,     The Warren Alpert Medical School of Brown University, Providence, RI, United Sates

Mahshid Imankhan,     Tehran Azad University of Medical Sciences, Tehran, Iran

Alexander S. Imas,     Department of Orthopedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

Shreya Jain,     College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Meghana Jami,     Johns Hopkins Medicine, Baltimore, MD, United States

Kyleen Jan

Midwest Orthopaedics at Rush, Chicago, IL, United States

Department of Sports Medicine, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States

Che Hang Jason Wong,     Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

Andrew Jawa

Department of Orthopaedic Surgery, New England Baptist Hospital, Tufts University School of Medicine, Boston, MA, United States

Boston Sports and Shoulder Center, Waltham, MA, United States

Thelma R. Jimenez Mosquea

Universidad Iberoamericana (UNIBE), Santo Domingo, Dominican Republic

Department of Orthopedic Surgery, NYU Langone Health, New York, NY, United States

Pinak Joshi

CareDx, Inc., San Francisco, CA, United States

Regis College, Weston, MA, United States

Sneha Kamada,     Biomedical Engineering Department, Johns Hopkins University, Baltimore, MD, United States

Kevin K. Kang,     Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

Hafiz F. Kassam

Hoag Orthopedic Institute, Irvine, CA, United States

UC Davis Medical Center, Davis, CA, United States

Nabil Z. Khan,     Department of Orthopedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

James A. King,     Provincial Research Data Services, Alberta Health Services, Centre for Health Informatics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

Christopher Klifto,     Department of Orthopedic Surgery, Duke University, Durham, NC, United States

Rebecca Knebels,     Inova Health System Sports Medicine Concussion Clinic, Musculoskeletal Service Line, Fairfax, VA, United States

Christopher Koch,     George Fox University, Newberg, OR, United States

Melissa K. Kossman,     School of Health Professions, University of Southern Mississippi, Hattiesburg, MS, United States

Ezan Kothari,     The University of Alabama at Birmingham, Department of Orthopaedic Surgery, Birmingham, AL, United States

Thomas J. Kremen Jr. ,     Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States

Laura M. Krivicich,     Department of Sports Medicine, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States; Midwest Orthopaedics at Rush, Chicago, IL, United States

Kristen L. Kucera

Department of Exercise and Sport Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

National Center for Catastrophic Sport Injury Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

Christopher M. Kuenze,     Department of Kinesiology, University of Virginia, Charlottesville, VA, United States

Michael Kutschke,     Brown University Warren Alpert School of Medicine, Providence, RI, United States

Salomon Abuchaibe Lacouture,     Medicine, Universidad del Norte, Barranquilla, Colombia

Natalia Andrea Lacouture Cardenas,     Atlantico, Universidad del Norte, Barranquilla, Colombia

Aaron Lam,     Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

Fabiola Langner Salinas,     Neuropathology Department, General Hospital of Mexico, Mexico City, Mexico

Adam S. Lepley

School of Kinesiology, University of Michigan, Ann Arbor, MI, United States

Exercise and Sport Science Initiative, University of Michigan, Ann Arbor, MI, United States

Laura Libreros-Peña

Centro de Investigaciones Clínicas, Fundación Valle Del Lili, Cali, Colombia

Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia

Jonathan Liu,     Brown University Warren Alpert School of Medicine, Providence, RI, United States

Sean Liu,     Dartmouth Geisel School of Medicine, Hanover, NH, United States

Ryan Lohre,     Department of Orthopaedic Surgery, Harvard Medical School, Massachusetts General Hospital, Boston Shoulder Institute, Boston, MA, United States

Tyler A. Luthringer,     Rothman Orthopaedic Institute, Philadelphia, PA, United States

Matthew Magruder,     Department of Orthopaedic Surgery, Maimonides Health, Brooklyn, NY, United States

Bhargavi Maheshwer,     Department of Orthopaedic Surgery, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, United States

Karen Manzur-Pineda,     Elsevier, Fort Lauderdale, FL, United States

Stephen E. Marcaccio,     Department of Orthopaedic Surgery, Brown University, Providence, RI, United States

Karen J. Martínez-Robles,     Maternal-Infant Studies Center, University of Puerto Rico, Río Piedras, PR, United States

Anette Paulin Mercado Rueda,     Barranquilla, Atlántico, Colombia

Patrick Mescher,     Uniformed Services University-Walter Reed National Military Medical Center, Department of Surgery, Division of Orthopaedics, Bethesda, MD, United States

Alexander Mihas,     Florida International University Herbert Wertheim College of Medicine, Miami, FL, United States

Jacob D. Mikula,     Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD, United States

Jacob D. Miller,     The University of Toledo Medical Center, Toledo, OH, United States

John D. Milner,     Department of Orthopaedic Surgery, Brown University, Warren Alpert School of Medicine, Providence, Rhode Island, United States

Kevin Moattari

Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

College of Medicine, State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, NY, United States

Alia J. Mowery,     Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, United States

Anand M. Murthi,     Shoulder and Elbow Surgery, Department of Orthopaedic Surgery, MedStar Union Memorial Hospital, Orthopaedic Surgery, Georgetown University School of Medicine, Baltimore, MD, United States

Farah N. Musharbash,     Department of Orthopaedic Surgery, The Johns Hopkins School of Medicine, Baltimore, MD, United States

Electra Nassis,     College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Mitchell K. Ng,     Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

Shane J. Nho

Department of Sports Medicine, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States

Midwest Orthopaedics at Rush, Chicago, IL, United States

Grant E. Norte,     College of Health and Human Services, University of Toledo, Toledo OH, United States

Chinemerem Nwosu,     School of Medicine, Duke University, Durham, NC, United States

Arnold Ocoro Vallecilla,     Mount Sinai Medical Center Florida, Miami Beach, FL, United States

Manuel A. Orellana,     Harbor-UCLA Medical Center, Los Angeles, CA, United States

Ibukunolowa Oshobu,     Medicine, All Saints University School of Medicine, Roseau, Dominica

José Carlos Padilla,     Dell Medical School, The University of Texas at Austin, Austin, TX, United States

Noorulain Paracha

Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Sneha Patel

Maimonides Medical Center, Department of Orthopaedic Surgery, Brooklyn, NY, United States

College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Ryan W. Paul,     Department of Orthopaedic Surgery, Division of Sports Medicine, Rothman Orthopaedic Institute, Philadelphia, PA, United States

Paula Andrea Pereira Zapata,     University of Antioquia, Medellin, Colombia

Evelyn E. Peña-Zárate,     Centro de Investigaciones Clínicas, Fundación Valle Del Lili, Cali, Colombia

Alexander P. Philips,     Warren Alpert Medical School of Brown University, Providence, RI, United States

Stephan G. Pill,     Department of Orthopaedic Surgery, Prisma Health - Upstate, Steadman Hawkins Clinic of the Carolinas, University of South Carolina Greenville School of Medicine, Greenville, SC, United States

Nicolas Piuzzi,     Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, OH, United States

Theodore Quan,     Department of Orthopaedic Surgery, Johns Hopkins, Columbia, MD, United States

Matthew Quinn,     Department of Orthopaedic Surgery, Brown University, RI, United States

Travis R. Quinoa,     Department of Neurological Surgery, Rutgers New Jersey Medical School, Newark, NJ, United States

Sina Ramtin,     Department of Surgery and Perioperative Care, Dell Medical School, University of Texas at Austin, Austin, TX, United States

Afshin E. Razi

Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Alexander J. Rondon,     Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA, United States

Daniela Russi-Pulgar,     Universidad del Norte, Barranquilla, Colombia

Maarouf Saad

Hoag Orthopedic Institute, Irvine, CA, United States

UC Davis Medical Center, Davis, CA, United States

Samir Sabharwal,     Department of Orthopaedic Surgery, Johns Hopkins Hospital, Baltimore, MD, United States

Giovanni Sanchez

Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

James Sanders,     Department of Orthopaedic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

Cassandra Sanko,     Department of Orthopaedic Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, United States

Armaan Shah,     College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Jesse Shaw,     Department of Family and Sports Medicine, Oregon Health & Science University, Portland, OR, United States; Oregon Health and Science University, Department of Neurology/Sports Medicine, Portland, OR, United States; University of Western States, College of Graduate Studies - Sports Medicine, Portland, OR, United States; Sparta Science, Clinical Research, Menlo Park, CA, United States

Bhavya K. Sheth,     Department of Orthopedic Surgery, Maimonides Medical Center, Brooklyn, NY, United States

Divya K. Sheth,     Department of Medical Engineering, University of South Florida, Tampa, FL, United States

Brendan Y. Shi,     Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States

Rohanit Singh,     Johns Hopkins Medicine, Baltimore, MD, United States

Margaret A. Sinkler,     Department of Orthopaedic Surgery, Case Western Reserve University, University Hospitals, Cleveland, OH, United States

David H. Sohn,     Shoulder and Sports Medicine, Orthopedic Surgery, University of Toledo Medical Center, Toledo, OH, United States

John Hayden Sonnier,     Department of Orthopaedic Surgery, Division of Sports Medicine, Rothman Orthopaedic Institute, Philadelphia, PA, United States

Uma Srikumaran,     Quality, Safety, & Service, Department of Orthopaedic Surgery, Johns Hopkins School of Medicine, Columbia, MD, United States

Varun Sriram,     University of California, Los Angeles, CA, United States

Kurt Edward Stoll,     Rothman Institute, Philadelphia, PA, United States

Alyssa Strassburg,     Department of Orthopaedic Surgery, NYIT College of Osteopathic Medicine, Old Westbury, NY, United States

Camille Sullivan,     Department of Orthopaedic Surgery, University of California, San Francisco, CA, United States

Krishna V. Suresh,     Johns Hopkins University Hospital, Department of Orthopaedic Surgery, Columbia, MD, United States

Sukrit Suresh,     Orthopaedic Surgery, Johns Hopkins Hospital, Baltimore, MD, United States

Claudia Sofía Tamayo-Torres,     Faculty of Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia

Edward J. Testa,     Department of Orthopaedic Surgery, Brown University, Warren Alpert School of Medicine, Providence, Rhode Island, United States

Semran B. Thamer,     Dartmouth Geisel School of Medicine, Hanover, NH, United States

Cameron G. Thomson,     Department of Orthopaedics, Warren Alpert Medical School at Brown University, Providence, RI, United States

Julie Titter,     Department of Orthopaedic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

Timothy Torrez,     The University of Alabama at Birmingham, Department of Orthopaedic Surgery, Birmingham, AL, United States

Kristin Toy,     Department of Orthopaedic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

Meaghan Tranovich,     Department of Orthopedics, Adena Orthopedic and Spine Institute, Chillicothe, OH, United States

Rushabh M. Vakharia,     Department of Orthopaedic Surgery, Maimonides Health, Brooklyn, NY, United States

Nicolás Valentino

Department of Orthopaedic Surgery, Maimonides Health, Brooklyn, NY, United States

College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Laura Valenzuela-Vallejo,     School of Medicine and Health Sciences, Universidad Del Rosario, Bogota, Colombia

Carola F. van Eck,     Sequoia Institute for Surgical Services Inc., Visalia, CA, United States

Priscilla Varghese,     College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Vahe Varzhapetyan,     Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Alayna K. Vaughan,     Rothman Orthopaedic Institute, Philadelphia, PA, United States

Perri Vingan,     College of Medicine, State University of New York (SUNY) Downstate, Brooklyn, NY, United States

Tarun K. Vippa,     Eastern Virginia Medical School, Norfolk, VA, United States

Kevin Williams,     The University of Alabama at Birmingham, Department of Orthopaedic Surgery, Birmingham, AL, United States

Tyler Williamson,     Centre for Health Informatics, Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

Melissa Womble,     Inova Health System Sports Medicine Concussion Clinic, Musculoskeletal Service Line, Fairfax, VA, United States

Melissa A. Wright

Department of Orthopedic Surgery, MedStar Union Memorial Hospital, Baltimore, MD, United States

Department of Orthopedic Surgery, Georgetown University School of Medicine, Washington, DC, United States

Shannon Y. Wu,     David Geffen School of Medicine at UCLA, Los Angeles, CA, United States

Diamantis Xylas,     Catalio Capital Management, New York, NY, United States

Anamaria Yañez-Sarmiento,     Facultad de Ciencias de la Salud, Universidad Icesi, Cali, Colombia

Lubna Ziauddin

Department of Sports Medicine, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States

Midwest Orthopaedics at Rush, Chicago, IL, United States

Preface

Translational research is essential to the advancement of Sports Medicine. Written for clinicians, scientists, students, and biotech/medtech entrepreneurs, this Sports Medicine–specific guide to translational research serves as a practical, step-by-step roadmap for designing and conducting basic, translational, and clinical research, including basic regulatory considerations for new technologies. Translational Sports Medicine aims to help bridge the gap between clinical problems, research, and practice. Comprehensively spanning from preclinical research, clinical research, clinical implementation, to public health, this book provides a clear process for understanding, designing, executing, and analyzing clinical and translational research.

The reader will learn how to more critically evaluate the quality of published studies with respect to measuring outcomes and to make effective use of all types of evidence in patient care. This book covers the principles of evidence-based medicine and applies these principles to the design of translational investigations.

This book's straightforward approach aims to help the aspiring investigator navigate challenging considerations in study design and implementation. Researchers will benefit from greater confidence in their ability to initiate and execute investigations along the translational spectrum, gain valuable insights on funding, avoid common pitfalls, and know what is needed in collaborators.

Whether you're a basic scientist with a promising therapeutic agent interested in moving from laboratory to clinical experimentation, an engineer needing to complete a pilot study for a new biomedical device, a student learning the principles of statistics or epidemiology, a clinician orchestrating and preparing grants for a randomized clinical trial, or an entrepreneur seeking insight on regulatory considerations, Translational Sports Medicine is a practical guide for effectively advancing and translating a Sports Medicine research question.

Adam E. M. Eltorai

Editor

Part I

Introduction

Outline

Introduction

Chapter 1. Introduction

Chapter 2. The translational process

Chapter 3. Scientific method

Chapter 4. Basic research

Part I Introduction

David H. Sohn

Shoulder and Sports Medicine, Orthopedic Surgery, University of Toledo Medical Center, Toledo, OH, United States

Chapter 1: Introduction

Jaewon Chang, and Joseph Guettler     William Beaumont Hospital, Department of Orthopaedic Surgery, Sports Medicine Division, Royal Oak, MI, United States

Abstract

Imagine a multitrack train system, each track with its own train heading toward the same destination. Each train has a train engineer who has a different educational background and has a vague idea that if they follow the track they are on, they will reach their destination. Because of their different educational backgrounds, the train engineers have better knowledge of certain parts of the journey and not so much on other parts. Each train has different baggage, engines, conductors, and different kinds of resources on board all with similar qualities. However, none of the train engineers know that each train is heading toward the same location. Each train represents different background groups of people with diverse skills biology, chemistry, computer science, engineering, medicine, and public health. Translational medicine is the multistep process of bringing all these unique backgrounds into a more streamlined process in the form of diagnostics, medical procedures, devices, and behavioral changes.

Keywords

Behavioral changes; Diagnostics; Education background; Medical procedures; Multitrack train system; Translational medicine

Imagine a multitrack train system, each track with its own train heading toward the same destination. Each train has a train engineer who has a different educational background and has a vague idea that if they follow the track they are on, they will reach their destination. Because of their different educational backgrounds, the train engineers have better knowledge of certain parts of the journey and not so much on other parts. Each train has different baggage, engines, conductors, and different kinds of resources on board all with similar qualities. However, none of the train engineers know that each train is heading toward the same location. Each train represents different background groups of people with diverse skills biology, chemistry, computer science, engineering, medicine, and public health. Translational medicine is the multistep process of bringing all these unique backgrounds into a more streamlined process in the form of diagnostics, medical procedures, devices, and behavioral changes.

Translational medicine is one of the youngest sciences. It encompasses a patient-focused approach in each step of the research process, and this includes breaking down the barriers between diagnosis, treatment, and device implementation. This new science has arisen from the large gap that now exists between medical teaching and pre-clinical research and the finality of the actual clinical application.

The technical definition of translation is the process of moving something from one place to another. In translational medicine, this means the moving of medical research from a prediction to an application. The difficulty of this arises from the complicated process of pre-clinical research, coupled with differences between in vitro conditions, animal models (rats, rabbits, etc.), and the hope of eventual human application.

For example, in vitro studies relating to regenerative cartilage procedures such as autologous chondrocyte implantation (ACI) and the newer generation known as matrix-induced autologous chondrocyte implantation (MACI)—show that the chondrocytes are not able to form hyaline cartilage and have little ability to break down the membrane or fibrin which are necessary to implant in vivo. ¹ Yet clinically there are many of us who have done second looks following these procedures and clearly see something arthroscopically that looks pretty darn close to normal cartilage.

The difference between in vivo and in vitro is obvious with the strict limited outside factors. Even when comparing in vitro to a human application, the difference in genotype and phenotype are obvious and it is sometimes hard to translate research from species to species. For example, with regards to bone healing, nonspecific and COX-2 selective nonsteroidal anti-inflammatory drugs have been shown to effect bone healing in animal studies and some selective human studies. However, it is difficult to extrapolate this information related to proper dosing—much less the actual benefits of this treatment on bone healing in human subjects. ²

Another gap exists that prevents new research discoveries from reaching their highest potential with patients especially in a timely manner. Even when discoveries of drugs and other interventions have been found to have positive outcomes, the formulary or compounding might be different from company to company with secret formularies that are held from true potential discovery. An example of this is platelet-rich plasma (PRP) injections that have been found to provide multiple benefits ranging from ulcer healing to rotator cuff repair. ³ The different formularies for each use of PRP differ from the company and from site usage.

A multitude of formularies applied to differing conditions and settings ends up producing a wide range of results and outcomes, resulting in the clouding of any actual potential for this intervention. ⁴ Ultimately, the potential of PRP has yet to be unlocked. However, the different tracks make it difficult for the research to reach the destination of clinical application because it is made more difficult by the way we analyze, qualify, and apply our research.

And by the time we exclude the thousands of studies and mountains of data that are not double-blinded randomized placebo-controlled clinical studies, we are left with only a handful of qualified studies. With such limited qualifying data we are often left in sports medicine to scientifically question some of our most successful procedures. Simple questions that we empirically know the answer to such as Does rotator cuff repair actually work? or Does ACL reconstruction improve knee function? become difficult to answer and prove based on the paucity of qualified studies coupled with the inability to apply these mountains of additional data. Even our national societies struggle with simple position statements and Clinical Practice Guidelines relating to common and clinically successful procedures because of barriers relating to the application of experienced clinical knowledge to the scientific formula.

Over the next number of chapters, the basics that define a streamlined approach of pre-clinical thought and research to device development and medical treatments are laid out. Translational medicine as it relates to the field of sports medicine is defined. And hopefully, by the end of this book, the readers will have a clearer idea of how to take what we learn to what we know.

After all, the ultimate goal is one train, no stops, and one destination …

References

1. Cottrell J, O'Connor J.P. Effect of non-steroidal anti-inflammatory drugs on bone healing. Pharmaceuticals (Basel). 2010;3(5):1668–1693. doi: 10.3390/ph3051668 Published 2010 May 25.

2. Martinez-Zubiaurre I, Annala T, Polacek M. Behavior of human articular chondrocytes during in vivo culture in closed, permeable chambers. Cell Med. 2012;4(2):99–107. doi: 10.3727/215517912X647226 Published 2012 Aug 7.

3. Ramaswamy Reddy S.H, Reddy R, Babu N.C, Ashok G.N. Stem-cell therapy and platelet-rich plasma in regenerative medicines: a review on pros and cons of the technologies. J Oral Maxillofac Pathol. 2018;22(3):367–374. doi: 10.4103/jomfp.JOMFP_93_18.

4. Jo C.H, Kim J.E, Yoon K.S, et al. Does platelet-rich plasma accelerate recovery after rotator cuff repair? A prospective cohort study. Am J Sports Med. October 2011;39(10):2082–2090. doi: 10.1177/0363546511413454 Epub 2011 Jul 7. PMID: 21737832.

Chapter 2: The translational process

Michael B. DiCosmo ¹ , Meaghan Tranovich ² , and Katherine Coyner ¹       ¹ Department of Orthopaedic Surgery, University of Connecticut School of Medicine, Farmington, CT, United States      ²Department of Orthopedics, Adena Orthopedic and Spine Institute, Chillicothe, OH, United States

Abstract

Translational research is the process in which laboratory findings or clinical evidence is employed to develop interventions to improve public health. It aims to ensure that discoveries and basic science research can be advanced into human trials by providing the highest possible chance of success in achieving both safety and efficacy. However, it should be noted that this process is viewed as bidirectional as well as a continuum, a fact captured by the T0–T4 classification system. This framework puts emphasis on studies with applicable results that directly benefit human health and help to eliminate failures earlier in the process to reduce the overall cost of developing new ideas in medicine.

Keywords

Clinical trial; Evidence-based; Public health; Research continuum; Research dissemination; Translational research

Key points

• Translational research aims to foster the development of safe and efficacious research from the basic science stage into results that ultimately reach the level of directly benefiting human health in a quicker more efficient way.

• Translational research should be thought of as multidirectional or a continuous spectrum rather than unidirectional.

• The translational process involves the coordination of efforts between individuals or groups with different areas of expertise.

Why it matters

Translational research aims to ensure that discoveries and basic science research can be advanced into human trials by providing the highest possible chance of success in achieving both safety and efficacy. ¹ In doing so it not only ensures that new treatments and knowledge can reach patients or populations that they are intended to reach, but that they are implemented correctly. ² , ³ This framework puts emphasis on studies with applicable results that directly benefit human health and help to eliminate failures earlier in the process to reduce the overall cost of developing new ideas in medicine. ²–⁴

Translational research

The field of translational science is fairly new, but is rapidly being recognized as an important new approach to research. While there are differing views on the exact definition, at its heart, this term refers to the process in which laboratory findings or clinical evidence are employed to develop interventions to improve public health. ⁵ In medicine, this may be viewed as a bench-to-bedside progression whereby basic science knowledge is converted into new diagnostic or therapeutic tools for clinicians.

The successful institution of new practices requires translational science trainees to think outside the box and engage in multidisciplinary collaboration and community engagement to transfer knowledge from the bench to the bedside and ultimately the community. ⁶ Translation aims to facilitate the progression of research through different phases, allowing new treatments to more quickly and effectively reach the patients for whom they are intended. This also encompasses public health measures and population-based interventions. ² The translational process, therefore, involves the coordination of efforts between individuals or groups with different areas of expertise, from those involved strictly in laboratory and preclinical research to those involved directly in patient care, public health officials, and the patients themselves.

The growing significance of the field of translational science was reflected by the formation of the National Center for Advancing Translational Sciences (NCATS), a division of the National Institutes of Health, in 2011. ⁷ The Center seeks to improve the translational process by providing resources and support at all stages of development. Although there are many models for translational research the NCATS and University of Wisconsin Institute for Clinical and Translational Research (ICTR) provide a highly accepted T0–T4 research classification system (Table 2.1 and Fig. 2.1). ⁸ It should be noted that this process is viewed as bidirectional as well as a continuum (Fig. 2.2).

T0

The T0 phase of translational research aims to identify opportunities and approaches to a health problem or gap in knowledge. This is the basic discovery phase or basic science stage that consists of preclinical and animal studies. Studies that are classified as T0 translational research will help to define the problem and target population.

Table 2.1

T1

T0 translational studies create the framework to move into the T1 phase by providing the basic information needed to approach a solution to the previously defined problem. Studies classified as T1 translational research aim to move basic research into human research, including phase I clinical trials, case studies, and observational studies. ³ , ⁹ These types of studies focus on developing new methods for diagnosis, treatment, and/or prevention in a highly controlled setting. This stage can be broadly defined as a proof of concept stage and the goal is usually focused on obtaining data for regulatory approval of an intervention.

T2

T2 research is focused on applying research to patients. Before interventions or research applications can be used in practice, evidence-based guidelines must be created. Phase II and III clinical trials and controlled studies aim to determine the efficacy of new biomedical interventions on large groups of patients by comparing the new intervention to the current standard practice. ³ , ⁹ The goal of this phase of research is not only to prove the ability of an intervention or test but to also define the clinical utility by applying it to a specific population of patients. Lastly, T2 research begins to monitor safety and adverse effects so a risk profile can be created. Based on the results of T2 research, clinical guidelines are created to ensure the treatment or test is used appropriately and safely.

T3

Evidence-based guidelines are used in T3 studies to take research to the clinical practice level. The types of research in this phase include phase IV clinical trials, clinical outcome studies, and postmarketing safety investigations. T3 research is often considered the most difficult phase as it faces the problem of translating guidelines into clinical practice in addition to evaluating the safety and benefits of the intervention. ⁶ , ¹⁰ To foster spread and use of new evidence-based guidelines into practice, T3 research also includes: dissemination research, implementation research, and diffusion research. ⁹–¹²

T4

Phase T4 research focuses on the outcome and effectiveness of new evidence-based guidelines on large populations after they have been fully implemented. ³ , ¹⁰ Thus, meaning that this phase of research evaluates the benefit of new health policy to society. This is often done by surveillance studies that monitor the morbidity, mortality, benefits, and risks on a macro (public health) level to get a true assessment of the impact of the change in health policy. While T4 research can be seen as the final phase or culmination of translational research, it often leads to the generation of additional questions and hypotheses that can spark new T1 or T2 research. ³ This cyclic nature, in addition to areas of overlap between phases demonstrates the multidirectional or continuous nature of translational research (Fig. 2.2). ³

Figure 2.1  Diagram demonstrating the bidirectional stages of translational research from early research to population level outcomes and the goal or impact of each stage.

Figure 2.2  Illustration of the translational research spectrum demonstrating more holistic point of view.

Get started

The best way to get started is to familiarize yourself with the classification system of translational research. Focusing on where certain types of research fall along the spectrum and then on the goal of each phase. Get to know your disease or problem of focus through background research: what is currently known about the problem? What is yet to be discovered about the problem? The answers to those two fundamental questions will determine what phase of research is necessary to advance understanding and better human health. After discovering your desired area of focus, you and your team should identify an achievable goal. An achievable goal should be determined by taking a look at the resources you have and the strengths and weaknesses of your research team including experience and training. Having an achievable goal in mind can help attract potential partners (voluntary health organizations, academic institutions, or the private sector). Lastly, never stop preparing. You should constantly reexamine your team and your plan so you can learn from mistakes, adapt and improve.

Pitfalls to avoid

• Overemphasis on rapid translation: There is a worldwide attitude and emphasis on publishing studies as soon as possible whether it be for financial or academic reasons. Trying to push studies through the translational research spectrum too fast leads to technologies and applications being hurried into use without examining the ethical, political or societal consequences.¹³

• Overvaluing T1–T2 research: The bulk of funding tends to be allocated to T1 and T2 studies because there is a common viewpoint that a drug or intervention is the most desired and valuable product.¹⁴ However the true benefits to society are seen and discovered in T3 and T4 studies as they evaluate the efficacy, costs, and benefits of an intervention on the population level. While there is great value in discovering an intervention or diagnostic tool, without the data that T3 and T4 studies provide, it is difficult to create policy and practice-based changes and therefore difficult to make a widespread impact.

• Undervaluing the importance of training and mentoring: translational research can be quite complex and requires a high level of training in several fields.¹⁵ Ideally clinical scientists will have experience in the basic science laboratory and basic scientists will have experience in the clinical field. In addition to scientific complexities there comes legal, ethical, and political factors that influence funding and approval for interventions. Without proper knowledge of the field and training, it can be quite difficult to push studies through the translational research spectrum. This can be avoided by utilizing experienced mentors and training programs, including experienced researchers especially those with graduate degrees focused on translational research, who are becoming increasingly popular within research teams.¹³,¹⁵

Real-world examples

• A research study from Mengsteab et al. at the Connecticut Convergence Institute for Translation in Regenerative Engineering provides an example of T0 research. This study utilizes a rabbit-based animal model to create a bioengineered ACL matrix that is superior to the current standard of using tendon autografts or allografts.¹⁶

• A recent study by Li and colleagues examined the differential expression of mRNAs, microRNAs, and long non-coding RNAs in colon adenocarcinoma with the express purpose of identifying potential future targets for immunotherapy.¹⁷

• A randomized double-blind controlled trial performed by Millan-Orge et al. demonstrated implementation of a Mediterranean diet or a low fat diet in patients with coronary artery disease led to long-term improvements in microvascular endothelial function based on laser doppler flowmetry.¹⁸

References

1. What is Translational Research? UAMS Translational Research Institute. Accessed 28 December 2021. https://tri.uams.edu/about-tri/what-is-translational-research/.

2. Woolf S.H. The meaning of translational research and why it matters. JAMA. 2008;299(2):211–213. doi: 10.1001/JAMA.2007.26.

3. Zarbin M. What constitutes translational research? Implications for the scope of translational vision science and technology. Transl Vis Sci Technol. 2020;9(8):22. doi: 10.1167/TVST.9.8.22.

4. Fudge N, Sadler E, Fisher H.R, Maher J, Wolfe C.D.A, Mckevitt C. Optimising translational research opportunities: a systematic review and narrative synthesis of basic and clinician scientists' perspectives of factors which enable