Author: Stephen Glasser
Affiliation: University of Alabama, Birmingham
Publisher: Springer
Publication Date: 2008
ISBN 10: 1402084854
ISBN 13: 9781402084850
Edition: 1st


This book is designed to provide the "student" interested in clinical research a foundation upon which to build more advanced study. The book focuses on clinical trials, in contrast to the many excellent textbooks that address epidemiological research. With the recent interest in patient oriented research, this book should provide a knowledge base that is not necessarily covered in other texts. Chapters discussing the FDA's role in clinical research, Data Safety and Monitoring Boards, Postmarketing studies, the use of placebo controls, and a focus on clinical trials illustrates this point. In addition, new types of clinical research are evolving, and as such, this book discusses genetic, pharmacoepidemiologic, and implementation research. Finally, chapters on tips on how to write a grant, the mentoring process, and how to present ones research results are unique to this book. .

Table of Contents

Front Matter

  • Acknowledgements
  • Contributors
  • List of Abbreviations

Part I

    Clinical Research: Definitions, “Anatomy and Physiology,” and the Quest for “Universal Truth” 1

    • Introduction
    • Definition of Clinical Research
    • History of Clinical Research
    • References

    Introduction to Clinical Research and Study Designs

    • Sampling
    • The Linear-Semilinear Relationship of Biological Variables
    • Strength of Relationships
    • The Hypothesis
    • An Overview of the Common Clinical Research Designs
    • Discussion
    • References

    Clinical Trials*

    • Introduction
    • Ethical Issues
    • Randomization
    • Implications of Eligibility Criteria
    • Efficacy vs Effectiveness
    • Patient Compliance
    • Recruitment and Retention
    • Degree of Masking (Blinding)
    • Selection of Comparison Groups
    • Analytic Approach
    • Losses to Follow Up
    • Surrogate Endpoints
    • Selection of Endpoints
    • Trial Duration
    • The Devil Lies in the Interpretation
    • Conclusions
    • References

    Alternative Interventional Study Designs

    • Introduction
    • Traditional Versus Equivalence/Non-inferiority Testing
    • The Null Hypothesis in Equivalence/Non-inferiority Trials
    • N of 1 Trials
    • Factorial Designs
    • Case Crossover Design
    • Externally Controlled Trials (Before-After Trials)
    • Large Simple Trials (LSTs) and Prospective, Randomized, Open-Label, Blinded Endpoint Designs (PROBE)
    • References

    Postmarketing Research*

    • Introduction
    • FDA ‘Mandated or Negotiated’ Studies (Phase IV Studies)
    • Practice Based Clinical Experience Studies
    • Non FDA Studies
    • Equivalence and non-inferiority trials are discussed in chapters 3 and 4 Large Simple Trials
    • Prospective, Randomized, Open-Label, Blinded Endpoint (PROBE) Design
    • Surveillance Studies
    • Drug Utilization and Pharmacoeconomic Studies
    • Discussion
    • Appendix
    • References

    The United States Federal Drug Administration (FDA) and Clinical Research

    • Historical Considerations
    • The FDA Now
    • International Conference on Harmonization (ICH)
    • USA Drug Development Phases
    • FDA and Surgical Interventions
    • Adverse Event Reporting
    • The FDA and Advertising
    • References

    The Placebo and Nocebo Effect

    • Definition
    • Placebo Effect in Clinical Trials
    • Characteristics of the Placebo Effect
    • Mechanism of the Placebo Effect
    • Placebo Effect in Various Diseases
    • Clincial Trials and the Ethics of Using Placebo Controls
    • Conclusions
    • Summary
    • References

    Recruitment and Retention

    • Introduction
    • Recruitment Process
    • Failures in Recruitment
    • Differences in Dealing with Clinical Trial Patients
    • Why People Participate in Clinical Research
    • Types of Recruitment
    • Minority Recruitment
    • HIPPA
    • Summary
    • References

    Data Safety and Monitoring Boards (DSMBs)

    • Early Study Termination
    • Interim Analysis
    • Observational Study and Monitoring Boards (OSMBs)
    • References


    • Introduction
    • Definition
    • Weaknesses
    • Statistical and Graphical Approaches
    • Discussion
    • Conclusion
    • Evidence Based Medicine
    • References

Part II

    Research Methods for Genetic Studies

    • Important Principles of Genetics
    • Units of Genetic Measure
    • Terms and Basic Concepts in Genetic Epidemiology
    • Biological Specimen
    • Ethical, Legal and Social Implications (ELSI)
    • Measurable Outcome and Phenotype
    • General Methods in Clinical Genetic and Genetic Epidemiology Studies
    • Candidate Gene vs. Genome-wide Association Studies
    • Risk Quantification
    • Additional Applications of Genetic Studies
    • Major Issues and Limitations in Genetic Studies
    • Concluding Remarks
    • Recommended Readings
    • References

    Research Methods for Pharmacoepidemiology Studies

    • Selection of Study Design
    • Study Designs Common in PE
    • Descriptive Observational Studies
    • Case Report
    • Case Series
    • Ecologic Studies
    • Cross-Sectional Studies
    • Analytical Studies
    • Cross-Sectional Studies
    • Case-Control Studies (or Case-Referent Studies)
    • Cohort Studies
    • Hybrid Studies
    • Nested Case-Control Studies
    • Case-Cohort Studies
    • Case-Crossover Studies
    • Case-Time-Control Studies
    • Biases in PE
    • Summary
    • References

    Implementation Research: Beyond the Traditional Randomized Controlled Trial

    • Introduction
    • Overcoming Barriers to Evidence Implementation
    • Implementation Research Tools
    • Designing Implementation Research Studies
    • Summary
    • Exhibit: Rural Diabetes Online Care (RDOC)
    • Resources
    • References

    Research Methodology for Studies of Diagnostic Tests

    • Introduction
    • Bayes Theorem
    • Kappa Statistic (k)
    • Definitions
    • Ways of Determining Test Accuracy and/or Clinical Usefulness
    • References

Part III

    Statistical Power and Sample Size: Some Fundamentals for Clinician Researchers

    • Introduction
    • Fundamental Concepts
    • Conclusions
    • References

    Association, Cause, and Correlation

    • Introduction
    • Relative Frequencies and Probability
    • Generalizing from Samples to Populations
    • Relative Risk and Attributable Risk
    • Odds Ratio
    • Relative Risk Reduction (RRR) and Absolute Risk Reduction (ARR) and Number Needed to Treat (NNT)
    • Correlations and Regression
    • Causal Inference
    • References

    Bias, Confounding, and Effect Modification

    • Introduction
    • Bias
    • Confounding
    • Confounding vs. Effect Modification
    • References

    It’s All About Uncertainty

    • Introduction
    • Conceptual Issues in Estimation
    • Conceptual Issues in Hypothesis Testing
    • Univariate and Multivariate (Multivariable) Statistics
    • Bayesian Analysis
    • Selection of Statistical Tools (or Why Are There So Many Statistical Tests?)
    • References

    Grant Writing

    • Basic Tenets of Grant Writing
    • The Blueprint of a Research Grant
    • Writing the Research Grant
    • Types of NIH Research Funding
    • Reference

Part IV

    The Media and Clinical Research

    • Control of Information (The Embargo Rule)
    • References

    Mentoring and Advising

    • Mentoring vs. Advising
    • Guidelines for Faculty/Student Interactions
    • Advising
    • K23 and K24 Awards

    Presentation Skills: How to Present Research Results

    • Introduction
    • The Structure of a Presentation
    • Stages of a Speaker
    • Audiovisuals
    • The Question and Answer Period
    • Conclusion
    • References