Practical Biostatistics: A Friendly Step-by-Step Approach for Evidence-based Medicine
By Mendel Suchmacher and Mauro Geller
5/5
()
About this ebook
- Customized presentation for biological investigators with examples taken from current clinical trials in multiple disciplines
- Clear and concise definitions and examples provide a pragmatic guide to bring clarity to the applications of statistics in improving human health
- Addresses the challenge of assimilation of mathematical concepts to better interpret literature, to build stronger studies, to present research effectively, and to improve communication with supporting biostatisticians
Mendel Suchmacher
Mendel Suchmacher, MD, MSc, graduated in Pharmaceutical Medicine at Federal University of the State of São Paulo, is Board Certified in Internal Medicine and Hematology-Hemotherapy and member of the American College of Physicians. He holds teaching and research positions at prestigious Brazilian institutions: Professor of Clinical Immunology at Carlos Chagas Institute of Medical Graduation; Professor & Chairman of Microbiology and Immunology, and Research Fellow at Teresopolis University Medical School - UNIFESO; Professor & Coordinator of the Genodermatoses Sector of the Clinical Genetics Service at Federal University of Rio de Janeiro. Additionally, he is member of the clinical staff of Hospital Israelita Albert Einstein.
Related to Practical Biostatistics
Related ebooks
Concise Biostatistical Principles & Concepts: Guidelines for Clinical and Biomedical Researchers Rating: 0 out of 5 stars0 ratingsPractical Biostatistics: A Step-by-Step Approach for Evidence-Based Medicine Rating: 0 out of 5 stars0 ratingsIntroduction to Biostatistics with JMP (Hardcover edition) Rating: 1 out of 5 stars1/5Clinical Evidence Made Easy Rating: 4 out of 5 stars4/5Principles and Practice of Clinical Trial Medicine Rating: 4 out of 5 stars4/5Concise Epidemiologic Principles and Concepts: Guidelines for Clinicians and Biomedical Researchers Rating: 0 out of 5 stars0 ratingsThe Sourcebook for Clinical Research: A Practical Guide for Study Conduct Rating: 5 out of 5 stars5/5Translational Medicine: Tools And Techniques Rating: 0 out of 5 stars0 ratingsResearch in Medical and Biological Sciences: From Planning and Preparation to Grant Application and Publication Rating: 0 out of 5 stars0 ratingsTranslational Bioinformatics and Systems Biology Methods for Personalized Medicine Rating: 0 out of 5 stars0 ratingsAnalysis of Clinical Trials Using SAS: A Practical Guide, Second Edition Rating: 0 out of 5 stars0 ratingsPrecision Medicine and the Reinvention of Human Disease Rating: 0 out of 5 stars0 ratingsPatient Registry Data for Research: A Basic Practical Guide Rating: 0 out of 5 stars0 ratingsNovel Designs of Early Phase Trials for Cancer Therapeutics Rating: 0 out of 5 stars0 ratingsThe Practical Guide to Clinical Research and Publication Rating: 0 out of 5 stars0 ratingsMethods and Applications of Longitudinal Data Analysis Rating: 0 out of 5 stars0 ratingsPrinciples of Biomedical Informatics Rating: 0 out of 5 stars0 ratingsClinical Research Computing: A Practitioner's Handbook Rating: 0 out of 5 stars0 ratingsGlobal Health Informatics: How Information Technology Can Change Our Lives in a Globalized World Rating: 5 out of 5 stars5/5Emery and Rimoin’s Principles and Practice of Medical Genetics and Genomics: Clinical Principles and Applications Rating: 0 out of 5 stars0 ratingsUnderstanding Clinical Research: An introduction Rating: 0 out of 5 stars0 ratingsThe Design and Development of Novel Drugs and Vaccines: Principles and Protocols Rating: 0 out of 5 stars0 ratingsEconomic Evaluation in Genomic Medicine Rating: 0 out of 5 stars0 ratingsClinical Trial Management – an Overview Rating: 0 out of 5 stars0 ratingsThe Era of Artificial Intelligence, Machine Learning, and Data Science in the Pharmaceutical Industry Rating: 5 out of 5 stars5/5Design and Analysis of Experiments in the Health Sciences Rating: 0 out of 5 stars0 ratingsEpidemiology and Biostatistics: Practice Problem Workbook Rating: 0 out of 5 stars0 ratingsBiostatistics for Medical and Biomedical Practitioners Rating: 0 out of 5 stars0 ratings
Computers For You
Mastering ChatGPT: 21 Prompts Templates for Effortless Writing Rating: 5 out of 5 stars5/5Deep Search: How to Explore the Internet More Effectively Rating: 5 out of 5 stars5/5How to Create Cpn Numbers the Right way: A Step by Step Guide to Creating cpn Numbers Legally Rating: 4 out of 5 stars4/5Creating Online Courses with ChatGPT | A Step-by-Step Guide with Prompt Templates Rating: 4 out of 5 stars4/5SQL QuickStart Guide: The Simplified Beginner's Guide to Managing, Analyzing, and Manipulating Data With SQL Rating: 4 out of 5 stars4/5Practical Lock Picking: A Physical Penetration Tester's Training Guide Rating: 5 out of 5 stars5/5The Professional Voiceover Handbook: Voiceover training, #1 Rating: 5 out of 5 stars5/5Computer Science: A Concise Introduction Rating: 4 out of 5 stars4/5The Insider's Guide to Technical Writing Rating: 0 out of 5 stars0 ratingsThe Mega Box: The Ultimate Guide to the Best Free Resources on the Internet Rating: 4 out of 5 stars4/5Elon Musk Rating: 4 out of 5 stars4/5Grokking Algorithms: An illustrated guide for programmers and other curious people Rating: 4 out of 5 stars4/5Python Machine Learning By Example Rating: 4 out of 5 stars4/5Procreate for Beginners: Introduction to Procreate for Drawing and Illustrating on the iPad Rating: 0 out of 5 stars0 ratingsChatGPT Ultimate User Guide - How to Make Money Online Faster and More Precise Using AI Technology Rating: 0 out of 5 stars0 ratingsThe ChatGPT Millionaire Handbook: Make Money Online With the Power of AI Technology Rating: 0 out of 5 stars0 ratingsThe Data Warehouse Toolkit: The Definitive Guide to Dimensional Modeling Rating: 0 out of 5 stars0 ratingsUser Friendly: How the Hidden Rules of Design Are Changing the Way We Live, Work, and Play Rating: 4 out of 5 stars4/5101 Awesome Builds: Minecraft® Secrets from the World's Greatest Crafters Rating: 4 out of 5 stars4/5The Invisible Rainbow: A History of Electricity and Life Rating: 4 out of 5 stars4/5CompTIA Security+ Practice Questions Rating: 2 out of 5 stars2/5Everybody Lies: Big Data, New Data, and What the Internet Can Tell Us About Who We Really Are Rating: 4 out of 5 stars4/5
Reviews for Practical Biostatistics
1 rating0 reviews
Book preview
Practical Biostatistics - Mendel Suchmacher
Academic Press is an imprint of Elsevier
32 Jamestown Road, London NW1 7BY, UK
225 Wyman Street, Waltham, MA 02451, USA
525 B Street, Suite 1800, San Diego, CA 92101-4495, USA
First edition 2012
Copyright © 2012 Elsevier Inc. All rights reserved
No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher. Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone (+44) (0) 1865 843830; fax (+44) (0) 1865 853333; email: permissions@elsevier.com. Alternatively, visit the Science and Technology Books website at www.elsevierdirect.com/rights for further information
Notice
No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made.
Trademarks/Registered Trademarks
Brand names mentioned in this book are protected by their respective trademarks and are acknowledged.
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library
Library of Congress Cataloging-in-Publication Data
A catalog record for this book is available from the Library of Congress
ISBN: 978-0-12-415794-1
For information on all Academic Press publications visit our website at elsevierdirect.com
Typeset by MPS Limited, Chennai, India www.adi-mps.com
Printed and bound in United States of America
12 13 14 15 16 10 9 8 7 6 5 4 3 2 1
Foreword
Our increasing awareness of biological mechanisms that underlie disease has vastly increased the possibility of performing clinical trials, epidemiological studies, and tests of new approaches to diagnosis and treatment. This, in turn, raises a major need for the investigator to understand the statistical principles that underlie the design, execution, and data analysis related to clinical research studies. Dr. Suchmacher and Dr. Geller have provided a practical and highly approachable guide to biostatistics in their book Practical Biostatistics. The first section will guide the reader through the steps involved in clinical trial design, including design principles, sample size calculation, choosing the most appropriate test, and hypothesis testing. The presentation is both concise and highly pragmatic, and includes self-evaluation questions with annotated answers. The other sections cover a variety of biostatistical issues, such as association studies, benefit-risk analysis, evaluation of diagnostic tests, approaches to meta-analysis, and correlation and regression analysis.
Although this book will not substitute for the need to collaborate with colleagues who have formal training in biostatistics, it will go a long way towards preparing the clinical investigator to design and carry out better studies. It will also prepare the investigator to work more productively with biostatistical experts. This book answers a real need in clinical research, and will be a welcome addition to the training armamentarium for clinical investigators.
Bruce Korf
Wayne H. and Sara Crews Finley
Professor of Medical Genetics
Chair, Department of Genetics
University of Alabama at Birmingham
USA
Preface
Clinical research has been evolving worldwide at an accelerated pace, over the last 30 years. The growing number of published papers, motivated by postgraduate programs or sponsored by official research incentive programs or pharmaceutical companies, is paralleled by regulatory demands based on sound scientific quality standards, considered undetachable from their ethical nature.
Even though engaged healthcare professionals and students, as well as professional clinical researchers, strive to accomplish the high technical skills demanded, some of them face difficulties in mastering biostatistics tools. These tools are necessary to critically interpret and assess papers already published, as well as to correctly develop and publish their own.
Driven by our own professional demands, we have been facing the challenge of assimilating mathematical concepts through Biostatistics-specialized literature, personal guidance, and clinical trials reading. Over the years, we continually documented the lessons learned until we reached the point where we noticed we had accumulated a significant body of knowledge, shareable with our colleagues. We then decided to organize, review (with the aid of a biostatistician) and publish it. By providing the project with Microsoft Office's Excel 2010 resources, we were able to propose a bridge between Biostatistics and the common technology user.
Obviously, we do not mean to exhaust the subject through this publication, but simply to make a didactic reference available to all professionals committed to the development of healthcare sciences who need to assimilate Biostatistical knowledge. Let them know this source was written by healthcare professionals just like them, who face the same difficulties as theirs. As a consequence, they are able to better interpret the literature necessary to compose their own studies, improve communication with the supporting biostatistician, and present their research as proficiently as possible.
We hope we achieved our goal, and that this modest contribution might be helpful to our readers.
Mendel Suchmacher
Mauro Geller
Acknowledgments
My mother, for taking me by the hand up to the point I could go on with my own feet.
My wife Ester and my son Renan, who accepted sacrificing our shared time so that this project could become a reality.
Luiz Claudio S. Brillanti and Renan Suchmacher, for their contribution to cover art and illustrations.
Joshua Dahlben (NYU) for language review of the manuscript.
Our patients, the very reason this book came into existence.
Table of Contents
Cover Image
Title
Copyright
Foreword
Preface
Acknowledgments
Part I Introduction
Chapter 1. Study Type Determination
1.1 Epidemiological Studies
1.2 Analytical Studies
1.3 Summary of Study Types
Suggested Reading
Part II. Observational Studies
Chapter 2. Determination of Association Strength between an Exposure Factor and an Event in Observational Studies
2.1 Case–Control Studies
2.2 Cohort Studies
Chapter 3. Increasing Accuracy in Observational Studies
3.1 Stratified Analysis
3.2 Multivariable Analysis
Suggested Reading
Part III. Step-by-Step Biostatistics of a Clinical Trial
Chapter 4. Step 1: Investigator’s Hypothesis and Expression of its Corresponding Outcome
Chapter 5. Step 2: Estimation and Assessment of a Published Trial
5.1 Factors Influencing n Determination
5.2 n Calculation
5.3 Assessing n of a Published Trial
Chapter 6. Step 3: Organization of Variables and Endpoints
6.1 Qualitative Variables
6.2 Quantitative Variables
Chapter 7. Step 4: Measures for Results Expression of a Clinical Trial
7.1 Central Tendency Measures
7.2 Dispersal Measures
7.3 Position Measures: Quantiles
Appendix 7.1 How to Calculate Mean Using Microsoft Excel (Section 7.1.1)
Appendix 7.2 How to Trim
The Mean of Outliers (Section 7.1.1)
Appendix 7.3 How to Determine Median Using Microsoft Excel (Section 7.1.2)
Appendix 7.4 How to Determine Mode Using Microsoft Excel (Section 7.1.3)
Appendix 7.5 How to Calculate Standard Deviation Using Microsoft Excel (Section 7.2.2)
Appendix 7.6 How to Find the Exact BMI that Corresponds to the 90th Percentile using Microsoft Excel (Section 7.3)
Appendix 7.7 How to Put all BMIs in a Rank and Percentile
Perspective using Microsoft Excel (Section 7.3)
Chapter 8. Step 5: Determination of Normality or Non-Normality of Data Distribution
Appendix 8.1 How to Verify Normality of a Graph Curve Using Microsoft Excel
Chapter 9. Step 6: Hypothesis Testing
9.1 Parametric Tests for Independent and Dependent Samples
9.2 Nonparametric Tests
Chapter 10. Step 7: Correlating Sample Data with the General Population – 95% Confidence Interval
10.1 Point Estimation
10.2 Interval Estimation (95% Confidence Interval)
Appendix 10.1 How to Determine Confidence Intervals Using Microsoft Excel (Sample A)
Suggested Reading
Part IV. Additional Concepts in Biostatistics
Chapter 11. Individual and Collective Benefit and Risk Indexes Inferable from Intervention Studies
11.1 Treatment Effect Indexes
11.2 Clinical Decision Analysis Indexes
Chapter 12. Statistical Assessment of Diagnostic Tests for the Clinic
12.1 Detection Capacity Indexes
12.2 Diagnostic Significance Indexes
Chapter 13. Systematic Reviews and Meta-Analyses
13.1 Definitions
13.2 Systematic Review
13.3 Meta-Analysis
13.4 Options if Meta-Analysis Performance is not Advisable
13.5 Systematic Review/Meta-Analysis Limitations
13.6 Systematic Review/Meta-Analysis Stages Summary
13.7 Suggested Resources and Literary Sources
Chapter 14. Correlation and Regression
14.1 Correlation
14.2 Regression
14.3 Multiple Linear Regression
Appendix 14.1 How to Build a Scatterplot and to Add a Trend Line Using Microsoft Excel
Appendix 14.2 How to Calculate Pearson’s Correlation Coefficient Using Microsoft Excel
Appendix 14.3 How to Predict a Dependent Variable Using Microsoft Excel
Chapter 15. Per Protocol Analysis and Intention to Treat Analysis
Suggested Reading
APPENDIX. Microsoft Excel 2010 Basics
A.1 Structure and Main Features of a Microsoft Excel 2010 Worksheet
A.2 Location of Statistical Resources
A.3 Building a Plain Table
A.4 Building a Basic Chart
A.5 Building a Chart Out of a Table
A.6 Pivot Table
Suggested Reading
Glossary
Index
Part I. Introduction
Chapter 1 Study Type Determination
Part I
Introduction
The objective of Part I is to instruct the reader on how to choose the study type that best fits his or her research goals and material resources as well as how to determine the study type of a given paper.
Chapter 1
Study Type Determination
A crucial stage in research planning is to determine the most suitable study type, according to the investigator’s hypothesis (Chapter 4) and material resources available. A proposed classification of study types for epidemiological and clinical research is detailed in this chapter.
1.1 Epidemiological Studies
Epidemiological studies aim to establish the frequency of a condition in a given population. In this type of study, establishing reliable risk or etiological correlations is not possible because precise consistency between risk factors exposure or nonexposure, as well as between affected or nonaffected groups, cannot be achieved. For this reason, epidemiological studies remain mostly limited to measuring frequencies. Suspected risk correlations should be clarified through analytical studies.
Epidemiological studies can be classified into three types: ecological studies, cross-sectional studies, and longitudinal studies.
1.1.1 Ecological Studies
Ecological studies aim to determine the frequency of a given condition, supposedly associated with some environmental factor, during parallel or subsequent past time spans. For example, during the past 3 years, students from school A, which is located in an underprivileged district, have been presenting a higher frequency of upper respiratory virus infection compared to students from school B, which is located in a middle-class district, whose frequency is considered usual.
1.1.2 Cross-Sectional Studies
In cross-sectional studies, the frequency of a given condition in a naturally evolving population under a suspected exposure factor is analyzed, like a snapshot (Figure 1.1).
Figure 1.1 Schematic representation of cross-sectional study type.
1.1.3 Longitudinal Studies
In longitudinal studies, a cohort is followed for several years, or sometimes decades, in order to establish the frequencies of specific conditions and their correlation with environmental or other biological factors. Comparisons can be performed intrasubject or between different subjects, if possible. A classic example is the Framingham Heart Study, which began in 1948 with 5209 subjects and is currently in its third generation of participants. Knowledge on important environmental factors currently associated with cardiovascular risk, such as lifestyle (smoking, diet, and exercise) and aspirin use, has been derived from this study.
1.2 Analytical Studies
Analytical studies aim to establish correlation strength between a condition and a factor putatively associated with its origin and/or natural history. These types of studies are the main focus of this book and can be classified either as observational or intervention studies.
1.2.1 Observational Studies
In observational studies, the frequency of a condition in a population is studied under so-called natural
circumstances. As such, active intervention from the investigator on these circumstances is not applicable. The main objective of observational studies is to establish the degree of hazard for a certain condition in relation to a considered exposure factor. Submitting the observed population to real world
situations is its advantage. Its limitation is that it yields less accurate conclusions because uncontrolled variables and potential confounders may generate bias. Observational studies can be classified as case–control or cohort studies.
Case–Control Studies
In case–control studies, two groups are retrospectively compared, according to the following model: (1) One group with the condition (case) is subdivided into two subgroups – one exposed and the other nonexposed to a studied exposure factor; and (2) another group without the condition (control) is subdivided into two subgroups – one exposed and the other nonexposed to the same factor (Figure 1.2).
Figure 1.2 Schematic representation of a case–control study type.
Case–control studies aim to determine the odds of acquiring a condition under exposure to a considered factor. For example, the odds of miners presenting asbestos-associated lung fibrosis relative to the general population are 1.5:1. The advantages of case–control studies are that they are less expensive to perform compared to cohort studies and they can be performed immediately because they are generally retrospective. Also due to this latter aspect, their limitations are: poor control over the exposure factor, uncontrolled variables, and potential confounders. Given the fact they focus on the outcome and move back
toward the exposure factor, they are generally retrospective. Their inferred association