Principles and Practice of Clinical Research

by Gallin

• ISBN13: 9780122740657
• ISBN10: 0122740653
• Format: Hardcover
• Copyright: 2002-01-14
• Publisher: Elsevier Science & Technology

Summary

Principles and Practice of Clinical Researchlt;/b> is a comprehensive text which addresses the theoretical and practical issues involved in conducting clinical research. This book is divided into three parts: ethical, regulatory, and legal issues; biostatistics and epidemiology; technology transfer, protocol development and funding. It is designed to fill a void in clinical research education and provides the necessary fundamentals for clinical investigators. It should be of particular benefit to all individuals engaged in clinical research, whether as physician or dental investigators, Ph.D. basic scientists, or members of the allied health professions, as well as both students and those actively participating in clinical research. Key Features * Comprehensive review ranging from a historical perspective to the current ethical, legal and social issues and an introduction to biostatistics and epidemiology * Practical guide to writing a protocol, getting funding for clinical research, preparing images for publication and display * Cohesive and clear presentation by authors carefully selected to teach a very popular course at NIH * Excellent companion text for courses on clinical research

Table of Contents

Contributors	xi
Preface	xiii
Acknowledgments	xv
A Historical Perspective on Clinical Research
John I. Gallin
The Earliest Clinical Research	1	(1)
The Greek and Roman Influence	1	(1)
Middle Ages and Renaissance	2	(1)
Seventeenth Century	3	(1)
Eighteenth Century	4	(2)
Nineteenth Century	6	(3)
Twentieth Century and Beyond	9	(6)
PART I ETHICAL, REGULATORY, AND LEGAL ISSUES
Ethical Principles in Clinical Research
Christine Grady
Distinguishing Clinical Research from Clinical Practice	15	(1)
What Does Ethics Have to Do with Clinical Research?	15	(1)
History of Ethical Attention to Clinical Research	16	(3)
Ethical Principles and Guidelines for the Protection of Human Subjects of Research: the Belmont Principles	19	(4)
Special Issues in the Conduct of Randomized Clinical Trials	23	(2)
Summary	25	(2)
Researching a Bioethical Question
Ezekiel J. Emanuel
Types of Bioethical Issues	27	(1)
Types of Bioethical Research Methodologies	27	(1)
Examples of Important Bioethical Research	28	(6)
Special Considerations in Bioethical Research	34	(5)
Integrity in Research: Individual and Institutional Responsibility
Alan N. Schechter
Recent History of the Scientific Misconduct Issue	39	(1)
Responses of Government	40	(1)
Responses of the Scientific Community	41	(1)
Guidelines for the Conduct of Research	42	(1)
Definition of Scientific Misconduct	43	(1)
Authorship	44	(1)
Conflicts of Interest	44	(1)
Conclusions	45	(6)
Institutional Review Boards
Alison Wichman
Alan L. Sandler
Historical, Ethical, and Regulatory Foundations for Current Requirements for Research Involving Human Subjects	51	(3)
Institutional Review Boards	54	(6)
Clinical Researchers and IRBs	60	(1)
The Current IRB System Under Evaluation	60	(1)
Conclusion	61	(2)
Data and Safety Monitoring Boards
Lawrence M. Friedman
Description of Data and Safety Monitoring Board	63	(1)
Data and Safety Monitoring Board Functions	64	(1)
Data and Safety Monitoring Board Decision Making	65	(1)
Examples	65	(2)
Conclusions	67	(2)
Data and Data Management Clinical Trials
Jane Cassidy
Definitions	69	(1)
Roles and Responsibilities	70	(2)
Administrative Aspects	72	(5)
Research Records	77	(1)
Data Standardization Coding Systems	78	(1)
Quality Assurance	79	(1)
Audits	79	(2)
Audit Preparation	81	(2)
Data Analysis	83	(1)
Security	83	(1)
Archiving	84	(1)
Summary	84	(1)
Conclusion	84	(22)
Unanticipated Risk in Clinical Research
Stephen E. Straus
The Reasons	106	(1)
The Drug	107	(1)
The Target	108	(1)
The Trials	108	(2)
Cassandra Revealed	110	(1)
Extended Studies	110	(1)
FIAU Toxicity	111	(1)
Reassessing the Preclinical Studies	112	(1)
Research Oversight	113	(1)
The Investigations Begin	113	(1)
Scientific Misconduct	114	(1)
The FDA	115	(1)
The NIH	115	(1)
The Institute of Medicine	116	(1)
The Media	116	(1)
The Congress	117	(1)
The Law	118	(1)
Epilogue	118	(5)
The Regulation of Drugs and Biological Products by the Food and Drug Administration
Kathryn C. Zoon
Robert A. Yetter
Background	123	(1)
Mission, Organization, and Terminology	124	(2)
Drug and Biologic Life Cycle	126	(6)
Summary	132	(1)
Appendix	132	(1)
Legal Issues
Patricia A. Kvochak
Legal Issues Related to Informed Consent for Clinical and Research Care	133	(1)
Advance Directives/Substitute Consent	134	(2)
Children in Research	136	(1)
Medical/Research Records	137	(1)
Legal Liability	138	(1)
Conflict of Interest	139	(1)
Authorship/Rights in Data	140	(1)
Appendix: NIH Advance Directive for Health Care and Medical Research Participation	141	(5)
NIH Policy on the Inclusion of Women and Minorities as Subjects of Clinical Research
Eugene G. Hayunga
Vivian W. Pinn
NIH Policy	146	(1)
Focus on Scientific Considerations	147	(1)
Role of the NIH Office of Research on Women's Health	147	(1)
Role of Peer Review	148	(1)
Role of the Institutional Review Board	149	(1)
Role of Volunteers and Their Communities	150	(1)
Reaction of the Scientific Research Community	151	(1)
Demographic Data on Subject Enrollment	152	(2)
Identifying Differences between Women and Men	154	(1)
Women of Childbearing Potential and Pregnant Women	155	(1)
Future Questions	156	(1)
Conclusions	157	(6)
PART II BIOSTATISTICS AND EPIDEMIOLOGY
An Introduction to Biostatistics: Randomization, Hypothesis Testing, and Sample Size
Paul S. Albert
Craig B. Borkowf
Introduction	163	(1)
Issues in Randomization	164	(6)
Overview of Hypothesis Testing	170	(9)
Sample Size and Power	179	(8)
Design and Conduct of Observational Studies and Clinical Trials
Teri A. Manolio
Types of Epidemiologic Study Designs	187	(1)
Case Reports and Case Series	187	(1)
Prevalence Surveys or Cross-Sectional Studies	188	(2)
Case-Control Studies	190	(3)
Prospective or Longitudinal Cohort Studies	193	(2)
Causal Inference in Observational Studies	195	(1)
Clinical Trials	196	(3)
Conduct of Epidemiologic Studies: The Study Protocol	199	(8)
Small Clinical Trials
Mitchell B. Max
Where We Are In the Short History of Controlled Clinical Trials	207	(1)
Explanatory vs. Pragmatic Orientation in Clinical Trials: Implications for Study Design	208	(1)
Issues in Small Clinical Trials that Examine Both Disease Mechanism and Treatment Efficacy	209	(8)
Placebo Responses in Clinical Trials	217	(5)
Conclusion	222	(3)
Large Clinical Trials: Clinical Research Institutes
Robert M. Califf
History	225	(1)
Phases of Evaluation of Therapies	225	(1)
Critical General Concepts	226	(1)
Expressing Clinical Trial Results	227	(2)
Concepts Underlying Trial Design	229	(4)
Legal and Ethical Issues	233	(3)
Hypothesis Formulation	236	(2)
Publication Bias	238	(1)
Statistical Considerations	238	(2)
Meta-Analysis and Systematic Overviews	240	(1)
Understanding Covariates and Subgroups	241	(1)
Therapeutic Truisms	241	(1)
Study Organization	242	(4)
Integration into Practice	246	(1)
Controversies and Personal Perspective	246	(2)
The Future	248	(3)
Using Secondary Data in Statistical Analysis
Bradley D. Freeman
Eric P. Gerstenberger
Steven Banks
Charles Natanson
Techniques of Meta-Analysis	251	(2)
Meta-Analysis of Clinical Trials of Anti-Inflammatory Agents in Sepsis	253	(1)
Conclusions	254	(5)
An Introduction to Survival Analysis
Joanna H. Shih
Four Motivating Examples	259	(1)
Features of Survival Data	260	(1)
Survival Function	260	(1)
Comparing Two Survival Functions	261	(3)
Stratified Logrank Test	264	(1)
Proportional Hazards Model	265	(2)
Measures of Function and Health-Related Quality of Life
Lynn H. Gerber
Background About Quality of Life Indicators	267	(1)
Definition of Quality of Life	267	(1)
Applications for Quality of Life Measures	268	(1)
Structure of Quality of Life Measures	269	(1)
Criteria for Selection of Quality of Life Measures	270	(1)
Specific Quality of Life Instruments	270	(1)
Other Instruments to Consider	271	(1)
Importance of Quality of Life Measures for Health Care	271	(4)
Economic Analysis and Clinical Research
Martin L. Brown
Keven B. Knopf
Stephen E. Marcus
Joseph Lipscomb
Outline of the Chapter	275	(1)
The Evolving Field of Economics and Health	276	(1)
Economic Cost and Health	277	(2)
Types of Economic Analysis	279	(9)
Comparing Costs Across Time and Place	288	(4)
The Use of Models in Economic Studies	292	(2)
Economic Analysis and Clinical Trials	294	(14)
PART III TECHNOLGY TRANSFER, PROTOCOL DEVELOPMENT, AND FUNDING
Overview of Technology Development
Bruce Goldstein
Scenario: Disasters Waiting to Happen	308	(1)
The First and Biggest Mistake: Signing the Agreements	309	(2)
Agreements Not To Disclose: Trade-Secrets and the ``CDA''	311	(2)
Agreements to Transfer Materials	313	(6)
Collaboration and Inventions: The ``CRADA''	319	(4)
Proprietary Materials: The ``Materials-CRADA''	323	(1)
Trademarks and Copyrights for the Government Scientist	324	(3)
Conclusion	327	(2)
Technology Transfer
James Clifford Haight
What is Technology Transfer?	329	(1)
What is a Patent?	330	(1)
What is an Invention?	330	(1)
Who is an Inventor?	331	(2)
How to/Not to Disclose an Invention	333	(5)
Why Obtain a Patent?	338	(1)
When to Seek a Patent	338	(1)
Processing Employee Invention Reports at the NIH	339	(1)
Where to Obtain a Patent?	339	(1)
Statutory and Administrative Basis for Patents	340	(1)
Patent Attorneys and Agents	340	(1)
Preparing the Patent Application	340	(1)
Actions by the U.S. Patent Examiner	341	(2)
Appeals from Adverse Examiner's Decisions	343	(1)
U.S. Patent Interferences	344	(1)
International Treaties and Foreign Patents	344	(1)
Procedures Under The Patent Cooperation Treaty	345	(1)
The European Patent Convention	346	(1)
The European Patent Office	347	(1)
National Patent Offices	347	(1)
Patent Prosecution Fees	347	(1)
The Licensing Process	348	(1)
Rights in Government Funded Extramural Inventions	348	(1)
Inventions Made in Federal Laboratories	348	(1)
Joint Inventions With Non-PHS Co-inventors	348	(5)
Types of Licenses Available at the NIH	353	(6)
Appendix 1: Research Plan	359	(1)
Appendix 2: Exceptions or Modifications to This Crada	359	(1)
Summary of Key Points to Remember	359	(2)
Telemedicine Systems
Kenneth M. Kempner
Frank S. Govern
Robert L. Martino
Background	361	(4)
Common Architectures for Telemedicine	365	(2)
Early NIH Telemedicine Activities	367	(10)
Development of a Comprehensive NIH Telemedicine Infrastructure (1993-Present)	377	(4)
The National Effort to Advance Telemedicine Systems	381	(3)
Conclusions	384	(3)
Animal Models of Human Disease
Domenico Accili
What Does the Clinician Need to Know About Animal Models?	387	(1)
The Choice of an Animal Model	388	(1)
The Amazing Development of Mouse Molecular Genetics	389	(12)
Conducting and Evaluating Clinical Research on Complementary and Alternative Medicine
Wayne B. Jonas
Klaus Linde
Public Use of Complementary and Alternative Medicine	401	(1)
Conventional Physician Use of CAM	402	(1)
The Risks of CAM	402	(1)
Potential Benefits of CAM	402	(1)
Reasons for CAM Use	403	(1)
Research Evaluation Principles in Medicine	403	(5)
Goals and Their Design Elements in CAM Clinical Trials	408	(1)
Special Issues in Clinical Research on CAM	409	(6)
Evaluation of Specific CAM Practices	415	(5)
Developing Research Strategies for CAM	420	(7)
Preparing Scientific Images for Publication and Display
Christopher Vargas
Determining Your Needs	427	(1)
Image Resolution	428	(2)
Bitmapped versus Vector Images	430	(1)
Typography Basics	431	(1)
WYSIWYG	432	(1)
Image Acquisition and Editing	433	(1)
Image File Formats	433	(1)
Word Processing	434	(1)
Drawing Software	435	(1)
PostScript Illustration Programs	435	(1)
Desktop Publishing Software	436	(1)
Presentation Software	436	(1)
HTML Software	436	(1)
Conclusions	437	(2)
Writing a Clinical Protocol: The Mechanics
Eddie Reed
Antoinette Jones-Wells
The Very First Steps	439	(2)
Molecular Correlative Studies	441	(1)
Framing the Question Being Asked	442	(1)
Converting Problems into Assets	443	(1)
Allocation of Time and Effort	444	(1)
Elements of the Protocol Document	445	(2)
Terms to be Familiar With	447	(2)
Getting the Funding You Need to Support Your Research: Successfully Navigating the NIH Peer Review Process for Grants
Olivia T. Preble Bartlett
Elliot Postow
Overview of the NIH	449	(5)
The NIH Peer Review Process for Grants	454	(8)
Hints For Preparing Better Grant Applications	462	(9)
NIH Award Mechanisms For Support of Clinical Researchers at Various Stages in Their Careers	471	(3)
How to Stay Informed About the NIH Peer Review System	474	(1)
Appendix	475	(2)
Index	477