Translational Orthopedics

1st Edition - April 15, 2024
Editors: Jeffrey A. Bakal, Jack M. Haglin, Joseph Abboud, Joseph J. Crisco, Adam E.M. Eltorai
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 8 5 6 6 3 - 8
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 8 8 5 6 2 - 1

Translational Orthopedics: Designing and Conducting Translational Research covers the principles of evidence-based medicine and applies these principles to the design of translati… Read more

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Translational Orthopedics: Designing and Conducting Translational Research covers the principles of evidence-based medicine and applies these principles to the design of translational investigations. 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 orthopedics, and know what is needed in collaboration. Further, this title is an indispensable tool in grant writing and funding efforts.

The practical, straightforward approach helps the aspiring investigator navigate challenging considerations in study design and implementation. The book provides valuable discussions of the critical appraisal of published studies in translational orthopedics, 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 Orthopedist who has ever had a good clinical idea but not the knowledge of how to test it.

Cover image
Title page
Table of Contents
Handbook for Designing and Conducting Clinical and Translational Research
Copyright
List of contributors
Preface
Part I. Introduction
Chapter 1. Introduction
Definitions and objectives
Structure
How to use this book
Intervention development
Clinical emphasis
Limitations
Chapter 2. Translational process
Key points
Introduction section/why it matters
Translational research definition
Historical perspective
The process of translational research
T0: Basic and applied research
T1: Translation to humans
T2: Translation to patients
T3: Translation to practice
T4: Translation to community
Conclusion
Get started
Potential pitfalls
Examples
Chapter 3. Scientific method
Key points
Introductory section/Why it matters
Observation
Question
Hypothesis
Experiment
Analysis
Conclusion
Get started
Potential pitfalls
Examples of scientific method
Resources
Chapter 4. Basic research
Key points
Why it matters
Basic research and the “reductionist approach”
Disciplines of basic research
Get started
Part II. Pre-clinical
Chapter 5. Overview of preclinical research
Key points
Introduction section/why it matters
Get started
Potential pitfalls
Examples
Resources
Chapter 6. Formulating a researchable question: a critical step for facilitating good clinical research
Key points
Introduction
Getting started
Pitfalls to avoid
Additional resources
Chapter 7. Types of interventions: drug, device, diagnostic, procedural technique, or behavior change
Key points
Introduction
Getting started
Potential pitfalls
Resources
Chapter 8. Drug discovery
Key points
Why it matters?
Drug discovery
The drug discovery process
Disciplines and common lab methods and techniques
Major areas of current investigation
Three real-world examples of drug discovery
How to obtain funding and resources
Get started with drug discovery
Common mistakes and tips for drug discovery
Chapter 9. Drug testing
Key points
“Why it matters?”
Drug testing
Get started
Potential pitfalls
Real-world examples
Resources
Chapter 10. Device discovery and prototyping
Key points
Introduction
Background
Examples of medical device development in the literature
Chapter 11. Device testing
Key points
“Why it matters?”
Testing
FDA classification
Funding
Get started
Pitfalls to avoid
Chapter 12. Diagnostic discovery
Key points
Overview and definition
Solving an unmet need
Conceptualized solution
New versus better
Prototyping
Disciplines and common diagnostic tools
Recently published examples
Budgetary considerations
Pitfalls to avoid
Chapter 13. Diagnostic testing
Key points
Introduction
Quality
Utility
Translational considerations
Chapter 14. Other product types
Key points
“Why it matters?”
What the FDA covers1
Health software
Mobile health applications7
Artificial intelligence and machine learning in software as a medical device
Chapter 15. Procedural technique development
Key points
Introduction
Preclinical considerations and methodologies
Stages of procedural technique development
Phase 0: proof of principle
Phase 1: refinement and definition
Phase 2: dissemination
Phase 3: comparison with current standard treatment
Phase 4: surveillance and quality control
Conclusion
Chapter 16. Behavioral intervention
Key points
Introduction
Get started
Potential pitfalls
Examples of behavioral interventions
Resources
Part III. Clinical: Fundamentals
Chapter 17. Introduction to clinical research
Key points
Introduction
What is clinical research?
The importance of clinical research
What leads to an important change in clinical practice?
Conclusion
Get started
Potential pitfalls
Examples in the literature
Resources
Chapter 18. The question
Key points
Why does it matter?
Types of research questions
How to develop a question
Other considerations
Examples of bad, good, and great questions
Conclusion
Get started
Pitfalls
Examples in the literature
Resources
Chapter 19. Study population
Key points
Why it matters
Chapter 20. Outcome measurements
Key points
Introductory section/why it matters
Background
Types of outcomes measurements
Examples of outcome measurements in the literature
Get started
Chapter 21. Optimizing the question: Balancing significance and feasibility
Key points
Introduction
Get started
Potential pitfalls
Examples of feasibility
Resources
Part IV. Statistical principles
Chapter 22. Common issues in analysis
Key points
Introductory section/why it matters
Get started
Potential pitfalls and examples
Chapter 23. Basic statistical principles
Key points
Why it matters?
Basic statistical principles
Real-world examples
Get started
Potential pitfalls
Resources
Chapter 24. Distributions
Key points
Why it matters?
Distributions
Real-world examples
Get started
Potential pitfalls
Resources
Chapter 25. Hypotheses and error types
Key points
Why it matters
Hypotheses1
Type I and type II errors1–3
Examples of hypotheses in the literature
Get started
Chapter 26. Power
Key points
Introduction
Get started
Chapter 27. Regression
Key points
Why it matters
Linear regression4,5
Multiple regression4,5
Logistic regression6
Precautions4
Get started
Chapter 28. Continuous variable analyses
Key points
Why it matters
Continuous variables
T-test
Mann–Whitney U-test
Wilcoxon signed-rank test
Get started
Potential pitfalls
Resources
Chapter 29. Categorical variable analyses
Key points
Why it matters
Chi-squared test
Fisher exact test
The Cochran–Mantel–Haenszel test
Get started
Potential pitfalls
Resources
Chapter 30. Analysis of variance
Key points
Why it matters
ANOVA4–6
Get started
Chapter 31. Correlation
Key points
Background
Calculating the correlation coefficient
Important considerations with correlation
Examples of correlation in literature
Chapter 32. Biases
Key points
Why it matters
Overview of bias
Types of bias and how to avoid
Internal and external validity4
Conclusion
Case examples
Get started
Potential pitfalls
Examples of bias
Resources
Chapter 33. Basic science statistics
Key points
Background
Variables: qualitative and quantitative
Quantitative variables: discrete or continuous
Discrete and continuous variables
Statistics: descriptive analyses
Mean
Median
Mode
Statistics: inferential analyses
t-Test
Analysis of variance
Mann–Whitney and Kruskall–Wallis tests
Part V. Clinical: Study types
Chapter 34. Design principles
Key points
Introduction
Background
Example
Get started
Chapter 35. Case series
Key points
Background
Body
Get started
Chapter 36. Case control study
Key points
Introductory section/why it matters
Background
Benefits and limitations
Design your own study
Standard research team and funding
Get started
Chapter 37. Cohort study
Key points
Background
Benefits and limitations
Design your own study
Standard research team and funding
Get started
Chapter 38. Cross-sectional study
Key points
Why it matters?
Definition
Advantages and disadvantages of cross-sectional studies
Designing a cross-sectional study
Notable examples of cross-sectional studies
Research team personnel roles
Practical considerations on how to fund this study type
Get started
Chapter 39. Longitudinal study
Key points
Background
Chapter 40. Clinical trials
Key points
Background
Common mistakes
Get started
Chapter 41. Meta-analysis
Key points
Introduction/why it matters
Background
Study design
Conclusion
Get started
Potential pitfalls
Examples of meta-analysis
Resources
Chapter 42. Cost-effectiveness study
Key points
Background
Study design
Conclusion
Get started
Potential pitfalls
Examples
Resources
Chapter 43. Diagnostic test evaluation
Key points
Introduction
Benefits and limitations
Get started
Examples
Potential pitfalls
Standard research team
Budget considerations and how to fund
Resources
Chapter 44. Reliability study
Key points
Background
General model for testing reliability
Estimating reliability
Reliability in current literature
Chapter 45. Database studies
Key points
“Why it matters?”
Database studies
Real-world examples
Get started
Potential pitfalls
Resources
Chapter 46. Surveys and questionnaires
Key points/why it matters
Chapter 47. Qualitative and mixed methods
What is qualitative and mixed methods research?
Benefits and limitations of qualitative methods and mixed methods research
Designing and developing a qualitative and or mixed methods study
Standard research team personnel and roles
Budgetary considerations and funding
Part VI. Clinical trials
Chapter 48. Randomized controlled study
Key points
Why it matters?
Advantages
Disadvantages
Designing your own RCT
Practical considerations on securing funding
Get started
Chapter 49. Nonrandomized controlled study
Key points
Why it matters
Advantages
Disadvantages
Designing your own nonrandomized controlled trial
Practical considerations on securing funding
Get started
Chapter 50. Historical control
Key points
Why it matters
Benefits and limitations to a historical control
Design of a historical control study
Funding and logistics of setting up a historical control study
Get started
Chapter 51. Cross-over
Key points
Introduction
Background
Advantages to cross-over
Limitations to cross-over
Chapter 52. Withdrawal studies: Design, measures, classic example
Key points
Introduction
Study design
Outcome measurement
Examples in the literature
The study team
Financial considerations
Chapter 53. Factorial design
Key points
Why it matters?
What is a factorial design?
Pros and cons of factorial design
How to design a factorial study
Research team and roles in factorial design
Budgetary considerations
Pitfalls to avoid
Get started—actionable items
Chapter 54. Group allocation
Key points
Why it matters?
What is a group allocation design?
Pros and cons of group allocation
How to design a group allocation
Research team and roles in group allocation
Budgetary considerations
Pitfalls to avoid
Get started—actionable items
Chapter 55. Hybrid design
Keypoints
Why it matters?
What is a hybrid design?
Pros and cons of hybrid design
How to design a hybrid study
Research team and roles in hybrid design
Budgetary considerations
Pitfalls to avoid
Get started—actionable items
Chapter 56. Large pragmatic studies
Key points
Introduction
Example
Getting started
Limitations and pitfalls
Funding and resources
Chapter 57. An overview of adaptive clinical trials
Key points
Introduction
Why it matters
Get started
Research team personnel and roles
Budgetary considerations and funding procurement
Potential pitfalls
Resources
Chapter 58. Randomization
Key points
Introduction
Conclusions
Chapter 59. Blinding
Key points
Introduction
Get started: what is blinding?
Types of blinding
Potential pitfalls: when blinding is impossible
Conclusion
Chapter 60. Multicenter considerations
Key points
Introduction
History
Steps
Pitfalls
Examples of multicenter studies in the orthopedic literature
Conclusion/why it matters
Chapter 61. Registries
Key points
Introduction: what is a registry study?
What are the benefits of a registry study and why do they matter?
What are the limitations of a registry study?
What are the steps to designing such a study?
What are the key roles of a registry study?
Funding
Getting started
Examples
Resources
Chapter 62. Phases of clinical trials
Key points
Why it matters?
Phases of clinical trials
Chapter 63. The IDEAL framework
Key points
What is the IDEAL framework?
The IDEAL framework phases
Questions to ask
IDEAL flowsheet
Summary
Chapter 64. Artificial intelligence
Key points
“Why it matters?”
Artificial intelligence methodologies in clinical research
Designing your own clinical study using AI
Real-world examples
Research personnel and roles
Budgetary concerns and how to get funding
Get started
Common pitfalls
Resources
Chapter 65. Patient perspectives
Key points
Introduction
Part VII. Clinical: Preparation
Chapter 66. Sample size
Key points
Why is sample size important?
Type I error, type II error, and power
Estimating effect size
Calculating sample size
Retrospective power analysis
Get started
Pitfalls to avoid
Resources
Chapter 67. Budgeting
Introduction
Funding
Budget
Direct costs
Indirect costs
Conclusion
Chapter 68. Ethics and review boards
Key points
Ethics
Institutional review boards
Chapter 69. Regulatory considerations for new drugs and devices
Key points
Introduction
Drugs
Devices
Issues with regulatory agencies
Get started
Chapter 70. Funding approaches
Introduction
Financing sources
Successful grant applications
Getting started
Potential pitfalls
Summary and key points
Chapter 71. Subject recruitment
Key points
“Why it matters?”
Subject recruitment
Cross cultural recruitment
Subject retention
Challenges to subject recruitment and retention
Real-world examples
Get started
Chapter 72. Data management
Key points
Introductory section
Get started
Potential pitfalls
Chapter 73. Statistical software
Key points
Introduction
Factors to consider
Evaluation framework
Popular statistical software options
Get started
Pitfalls to avoid
Examples in the literature
Resources
Chapter 74. Report forms
Key points
Introduction
Types of clinical report forms
Data collection
Other considerations
Conclusion
Get started
Potential pitfalls
Examples of report forms
Resources: (Additional reading, consultants, contractors)
Chapter 75. Subject adherence
Key points
Why it matters?
Intention-to-treat versus per-protocol analyses
Benefits and drawbacks of ITT analysis
Benefits and drawbacks of PP analysis
Practical implementation of ITT and PP
Get started
Chapter 76. Survival analysis
Key points
Introduction
What is survival analysis
Why it matters?
Attrition in study sample3–7
Preparing a survival analysis strategy
Methods to calculate survival analysis
Pitfalls to avoid
Get started
Resources
Consultants
Chapter 77. Monitoring committee in clinical trials
Key points
Why it matters
Data monitoring committees
Creating a DMC
Get started
Additional reading
Part VIII. Regulatory basics
Chapter 78. The Food and Drug Administration
Key points
“Why it matters?”
What does the FDA do?
Is your product regulated?
FDA branches/divisions
Real-world examples
Get started
Potential pitfalls
Resources
Chapter 79. IND
Key points
Introduction
Categories of INDs
Preparation for submitting an IND application
IND application process
Responsibilities after submission
Get started
Potential pitfalls
Additional resources
Chapter 80. New drug application
Key points
“Why it matters?”
Overview
Process/pathway for a new drug application
Components
Common challenges of new drug applications/drug discovery
Budgetary considerations and how to fund new drug application/drug discovery
Real world examples
Get started
Potential pitfalls
Resources
Chapter 81. Devices
Key points
Why it matters?
Overview
Process/pathway
Examples
Common challenges/pitfalls
Budgetary considerations and how to fund
Getting started
Resources
Chapter 82. Radiation-emitting electronic products
Key points
Why it matters
Get started
Potential pitfalls
Examples
Chapter 83. Orphan drugs
Key points
Why it matters
Orphan drugs
Get started
Potential pitfalls
Real-world example
Resources
Chapter 84. Orthopedics journal: biologics
Key points
Overview
Additional reading, consultants, contractors
Chapter 85. Combination products
Key points
Introductory section/why it matters
Plasma spray coatings on orthopedic devices
Potential pitfalls
Examples of...
Chapter 86. Foods
Key points
Overview
Legislation and regulatory compliance
Common challenges
Budgetary considerations
Chapter 87. Cosmetics
Key points
Why it matters?
Overview
Process/pathway
Components
Examples
Common challenges
Budgetary considerations/how to fund
Getting started
Potential Pitfalls
Resources/further reading
Chapter 88. CMC and GxP
CMC
GxP
Chapter 89. Non-US regulatory guidelines
Key points
Why it matters?
Get started
Pitfalls to avoid
Additional reading
Chapter 90. Post-market drug safety monitoring
Chapter 91. Postmarket device safety monitoring
Key points
Introduction
Passive surveillance
Post-market clinical studies
Medical device registry
Device recalls
Postmarket device safety monitoring in orthopedics
Getting started
Potential pitfalls
Examples of postmarket device safety monitoring in orthopaedics
Resources
Part IX. Clinical implementation
Chapter 92. Implementation research
Key points
Why it matters?
What is implementation research?
Pros and cons of implementation research
How to design implementation research
Research team and roles in implementation research
Budgetary considerations
Pitfalls to avoid
Get started—actionable items
Chapter 93. Design and analysis
Key points
Introduction
Get started
Examples of translational studies
Study trial designs and analysis
Chapter 94. Mixed methods research in implementation science
Key points
Why it matters
Implementation of research objectives and rationales
Two examples of mixed methods implementation research in orthopedics
Conclusion
Get started
Potential pitfalls
Additional resources
Chapter 95. Population and setting-specific implementation
Key points
Introductory section/why it matters
Background
Unique considerations
Successful approaches
Examples from the literature
Practical considerations in how to fund this stage
Get started
Part X. Public health
Chapter 96. Public health
Key points
Introduction
Get started
Pitfalls to avoid
Chapter 97. Epidemiology
Key points
Introductory section/why it matters
Get started
Potential pitfalls
Resource
Overview
Objectives
Principles
Epidemiologic methods
Experimental studies
Advantages and limitations
Examples of experimental studies
Conclusion
Chapter 98. Public health factors
Key points
Why it matters?
Get started
Pitfalls to avoid
Additional reading
Chapter 99. Good questions
Key points
Why it matters
Chapter 100. Population- and environmental-specific considerations
Key points
Introduction
Example 1: Health literacy
Example 2: Dimensions of accessibility and the application of telemedicine
Example 3: Racial and ethnic health disparities
Conclusion
Get started
Potential pitfalls
Resources
Chapter 101. Public health: Law policy and ethics
Key points
Introductory section/why it matters
Informed consent
Inclusion and exclusion criteria
Data integrity and methodology
Equity, diversity, and inclusion
Examples of legal requirements in medicine
Get started
Potential pitfalls
Resources
Chapter 102. Healthcare institutions and systems
Key points
Introductory section/why it matters
Get started
Potential pitfalls
Chapter 103. Public health institutions and systems
Key points
Introductory section/why it matters
Getting started
Potential pitfalls
Part XI. Practical resources
Chapter 104. Presenting data
Key points
Introduction
Background
Data presentation: text format
Data presentation: table format
Data presentation: graphical format
Chapter 105. Manuscript preparation
Key points
Approach
Writing clearly
Anatomy of a manuscript
Get started
Pitfalls to avoid
Examples in the literature
Resources
Chapter 106. Building a team
Key points
Introduction
Building a team
Starting a lab
Partnering with a researcher/clinician
Contract labs for hire
Getting started
Additional resources
Chapter 107. Patent basics
Key points
Introduction
Why it matters
What is a patent?
Considerations when applying for a utility patent
Get started
Potential pitfalls
Additional resources
Chapter 108. Venture pathways
Key points
Why it matters?
Basics of starting a company
Basics of licensing
Partnerships
Acquisition
Getting started
Pitfalls to avoid
Additional resources
Chapter 109. SBIR and STTR programs
Key points
Introduction
Eligibility
The phases of development
The nuances of applying
Get started
Potential pitfalls
Examples of SBIR/STTR success stories
Resources/suggested reading
Chapter 110. Sample forms and templates
Key points
Introductory section/why it matters
Get started
Potential pitfalls
Examples of
Glossary
Index

Jeffrey A. Bakal

Jeff Bakal PhD, P.Stat. is the Program Director for Provincial Research Data Services at Alberta Health Services which operates the Alberta Strategy for Patient Oriented Research (SPOR) data platform and Health Service Statistical & Analytics Methods teams. He has over 10 years of experience working with Health Services data and Randomized Clinical Trials. He completed his PhD jointly with the Department of Mathematics and Statistics and the School of Physical Health and Education at Queen's University. He has worked on the methodology and analysis of several international studies in business strategy, ophthalmology, cardiology, geriatric medicine and the analysis of kinematic data resulting in several peer reviewed articles and conference presentations. His current interests are in developing statistical methodology for time-to-event data and the development of classification tools to assist in patient decision making processes.

Affiliations and expertise

Division General Internal Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton Alberta, Canada

Joseph Abboud

Dr. Abboud is a Board Certified Orthopaedic Surgeon and specializes in the treatment of patients with shoulder and elbow disorders. He is an internationally recognized authority on the treatment of shoulder and elbow disorders. He is a Professor of Orthopaedic Surgery at the Sidney Kimmel Medical College of Thomas Jefferson University and a core member of the teaching faculty for Rothman Orthopaedics. Dr. Abboud received his medical degree with honors from Georgetown University School of Medicine and went on to complete his residency in Orthopaedic surgery at the Hospital of the University of Pennsylvania where he served as the administrative chief resident and received the award. He subsequently completed two (one-year) fellowships at the University of Pennsylvania in Shoulder and Elbow surgery and Orthopaedic Biomechanics. Dr. Abboud has published over 250 peer reviewed publications, given over 600 invited lectures nationally and internationally, and published several textbooks and numerous book chapters. He has received the prestigious Neer award and Burkhardt award for excellence in research. Dr. Abboud performs a wide variety of simple and complex surgical procedures on the shoulder and elbow including arthroscopic surgery (e.g. rotator cuff repairs, instability surgery) comprehensive fracture care, as well as shoulder and elbow replacement (arthroplasty) procedures. Dr. Abboud is most proud of the fact that he has been caring for patients throughout the Philadelphia region and the Northeast region of the United States. Patients seek out his care from all regions of the United States and overseas. His goal is to always provide each patient with exceptional personalized care.

Affiliations and expertise

Professor of Shoulder and Elbow Surgery Department of Orthopedics The Sidney Kimmel Medical College Thomas Jefferson University Chief Medical Officer Rothman Orthopedics Philadelphia, PA , USA

Joseph J. Crisco

Prof. J.J. Trey Crisco research interests are in musculoskeletal biomechanics where he focuses on upper extremity mechanics and osteoarthritis using advanced imaging analysis and on neuromuscular therapy. He also has an extensive interest in sports injury prevention and performance. His work has been primarily funded by the NIH and has resulted in over 200 peer-reviewed publications. He serves on several NIH study sections, editorial boards, and the scientific advisory committees of International Federation of Women's Lacrosse, US Lacrosse and USA Baseball. Prof. Crisco is a former Editor-in-Chief of the Journal of Applied Biomechanics and President of the American Society of Biomechanics. He has previously taught Basic Biomechanics and Product Design and Development, a joint effort between Industrial Design Department at RISD and Engineering at Brown University. He provides guest lectures and supports undergraduates for their independent studies and honors work, master's and doctoral students in his lab.

Affiliations and expertise

Henry Frederick Lippitt Professor of Orthopaedic Research; Executive Director for Research, Department of Orthopaedics; Director Bioengineering Laboratory, Department of Orthopaedics, The Warren Alpert Medical School of Brown University and Rhode Island Hospital, Providence, RI United States

Adam E.M. Eltorai

Adam E. M. Eltorai, MD, PhD completed his graduate studies in Biomedical Engineering and Biotechnology along with his medical degree from Brown University. His work has spanned the translational spectrum with a focus on medical technology innovation and development. Dr. Eltorai has published numerous articles and books.

Affiliations and expertise

Harvard Medical School, Boston, MA, USA

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Translational Orthopedics

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Jeffrey A. Bakal

Joseph Abboud

Joseph J. Crisco

Adam E.M. Eltorai