Designing Clinical Research

by Hulley, Stephen B.; Cummings, Steven R.; Browner, Warren S.; Grady, Deborah G.; Newman, Thomas B.

• ISBN13: 9780781782104
• ISBN10: 0781782104
• Edition: 3rd
• Format: Paperback
• Copyright: 2006-11-27
• Publisher: LWW

Summary

Designing Clinical Research sets the standard for providing a practical guide to planning, tabulating, formulating, and implementing clinical research, with an easy-to-read, uncomplicated presentation. This edition incorporates current research methodology--including molecular and genetic clinical research--and offers an updated syllabus for conducting a clinical research workshop. Emphasis is on common sense as the main ingredient of good science. The book explains how to choose well-focused research questions and details the steps through all the elements of study design, data collection, quality assurance, and basic grant-writing. All chapters have been thoroughly revised, updated, and made more user-friendly.

Table of Contents

Contributing Authors	xi
Introduction	xiii
Acknowledgments	xv
Section I: Basic Ingredients
Getting Started: The Anatomy and Physiology of Clinical Research	3	(14)
Anatomy of Research: What It's Made Of	3	(5)
Physiology of Research: How It Works	8	(5)
Designing the Study	13	(1)
Summary	14	(1)
Appendix 1.1: Outline of a Study	15	(1)
Reference	15	(2)
Conceiving the Research Question	17	(10)
Origins of a Research Question	18	(1)
Characteristics of a Good Research Question	19	(3)
Developing the Research Question and Study Plan	22	(1)
Translational Research	23	(2)
Summary	25	(1)
References	25	(2)
Choosing the Study Subjects: Specification, Sampling, and Recruitment	27	(10)
Basic Terms and Concepts	28	(1)
Selection Criteria	29	(3)
Sampling	32	(1)
Recruitment	33	(2)
Summary	35	(1)
Appendix 3.1: Selecting a Random Sample from a Table of Random Numbers	36	(1)
References	36	(1)
Planning the Measurements: Precision and Accuracy	37	(14)
Measurement Scales	38	(1)
Precision	39	(2)
Accuracy	41	(4)
Other Features of Measurement Approaches	45	(1)
Measurements on Stored Materials	46	(1)
In Closing	47	(1)
Summary	47	(1)
Appendix 4.1: Operations Manual: Operational Definition of a Measurement of Grip Strength	48	(1)
References	49	(2)
Getting Ready to Estimate Sample Size: Hypotheses and Underlying Principles	51	(14)
Hypotheses	51	(3)
Underlying Statistical Principles	54	(5)
Additional Points	59	(3)
Summary	62	(1)
References	63	(2)
Estimating Sample Size and Power: Applications and Examples	65	(32)
Sample Size Techniques for Analytic Studies and Experiments	65	(6)
Other Considerations and Special Issues	71	(2)
Sample Size Techniques for Descriptive Studies	73	(2)
What to do When Sample Size is Fixed	75	(1)
Strategies for Minimizing Sample Size and Maximizing Power	76	(5)
How to Estimate Sample Size When there is Insufficient Information	81	(1)
Common Errors to Avoid	82	(1)
Summary	83	(1)
Appendix 6A: Sample Size Required per Group When Using the t Test to Compare Means of Continuous Variables	84	(2)
Appendix 6B: Sample Size Required per Group When Using the Chi-Squared Statistic or Z Test to Compare Proportions of Dichotomous Variables	86	(3)
Appendix 6C: Total Sample Size Required When Using the Correlation Coefficient (r)	89	(1)
Appendix 6D: Sample Size for a Descriptive Study of a Continuous Variable	90	(1)
Appendix 6E: Sample Size for a Descriptive Study of a Dichotomous Variable	91	(1)
Appendix 6F: Use and Misuse of t Tests	92	(1)
References	93	(4)
Section II: Study Designs
Designing a Cohort Study	97	(12)
Prospective Cohort Studies	97	(2)
Retrospective Cohort Studies	99	(1)
Nested Case--Control and Case--Cohort Studies	100	(3)
Multiple-Cohort Studies and External Controls	103	(1)
Other Cohort Study Issues	104	(2)
Summary	106	(1)
References	106	(3)
Designing Cross-Sectional and Case-Control Studies	109	(18)
Cross-Sectional Studies	109	(3)
Case-Control Studies	112	(9)
Choosing Among Observational Designs	121	(1)
Summary	121	(1)
Appendix 8A: Calculating Measures of Association	122	(1)
Appendix 8B: Why the Odds Ratio Can Be Used as an Estimate for Relative Risk in a Case-Control Study	123	(2)
References	125	(2)
Enhancing Causal Inference in Observational Studies	127	(20)
Spurious Associations	127	(4)
Real Associations Other than Cause-Effect	131	(1)
Coping With Confounders in the Design Phase	132	(5)
Coping with Confounders in the Analysis Phase	137	(4)
Underestimation of Causal Effects	141	(1)
Choosing a Strategy	141	(2)
Summary	143	(1)
Appendix 9A: Hypothetical Example of Confounding and Interaction	144	(1)
Appendix 9B: A Simplified Example of Adjustment	145	(1)
References	146	(1)
Designing a Randomized Blinded Trial	147	(16)
Selecting the Intervention and Control Conditions	147	(3)
Choosing Outcome Measurements	150	(2)
Selecting the Participants	152	(2)
Measuring Baseline Variables	154	(1)
Randomizing and Blinding	155	(4)
Summary	159	(1)
References	160	(3)
Alternative Trial Designs and Implementation Issues	163	(20)
Alternative Clinical Trial Designs	163	(7)
Conducting a Clinical Trial	170	(9)
Summary	179	(1)
Appendix 11.1: Interim Monitoring of Trial Outcomes	180	(1)
References	181	(2)
Designing Studies of Medical Tests	183	(24)
Determining Whether a Test is Useful	183	(3)
Studies of Test Reproducibility	186	(2)
Studies of the Accuracy of Tests	188	(4)
Studies of the Effect of Test Results on Clinical Decisions	192	(1)
Studies of Feasibility, Costs, and Risks of Tests	193	(1)
Studies of the Effect of Testing on Outcomes	194	(2)
Pitfalls in the Design or Analysis of Diagnostic Test Studies	196	(3)
Summary	199	(1)
Appendix 12A: Calculation of Kappa to Measure Interobserver Agreement	200	(2)
Appendix 12B: Numerical Example of Verification Bias: 1	202	(1)
Appendix 12C: Numerical Example of Verification Bias: 2	203	(1)
References	204	(3)
Utilizing Existing Databases	207	(18)
Advantages and Disadvantages	207	(1)
Secondary Data Analysis	208	(3)
Ancillary Studies	211	(2)
Systematic Reviews	213	(5)
Summary	218	(1)
Appendix 13.1: Statistical Methods for Meta-Analysis	219	(1)
References	220	(5)
Section III: Implementation
Addressing Ethical Issues	225	(16)
Ethical Principles	225	(1)
Federal Regulations for Research on Human Subjects	226	(5)
Research Participants who Require Additional Protections	231	(1)
Responsibilities of Investigators	232	(3)
Ethical Issues Specific to Certain Types of Research	235	(1)
Other Issues	236	(1)
Summary	237	(1)
References	237	(4)
Designing Questionnaires and Interviews	241	(16)
Designing Good Instruments	241	(9)
Steps in Assembling the Instruments for the Study	250	(2)
Administering the Instruments	252	(1)
Summary	253	(1)
Appendix 15.1: An Example of a Questionnaire about Smoking	254	(1)
References	255	(2)
Data Management	257	(14)
Data Tables	257	(4)
Data Entry	261	(5)
Extracting Data (Queries)	266	(1)
Identifying and Correcting Errors in the Data	267	(1)
Analysis of the Data	268	(1)
Confidentiality and Security	268	(1)
Summary	269	(1)
References	269	(2)
Implementing the Study and Quality Control	271	(20)
Assembling Resources	272	(4)
Finalizing the Protocol	276	(3)
Quality Control During the Study	279	(7)
Summary	286	(1)
Appendix 17.1: Example of an Operations Manual Table of Contents	286	(1)
Appendix 17.2: Quality Control Tables and Checklists	287	(2)
References	289	(2)
Community and International Studies	291	(10)
Why Community and International Research?	291	(2)
Community Research	293	(1)
International Research	294	(5)
Summary	299	(1)
References	299	(2)
Writing and Funding a Research Proposal	301	(16)
Writing Proposals	301	(2)
Elements of a Proposal	303	(6)
Characteristics of Good Proposals	309	(1)
Finding Support for Research	310	(5)
Summary	315	(1)
References	316	(1)
Exercises	317	(14)
Answers to Exercises	331	(22)
Subject Index	353