Designing Clinical Research

This book is about the science of doing clinical research in all its forms: translational research,clinical trials, patient-oriented research, epidemiologic studies, behavioral science and health services research. Codifying the nature of this broad-based science and how to do it is not straightforward, and there is no single approach that everyone agrees is best. Our first two editions drew on the terms and principles of epidemiology in a practical and reader-friendly way, emphasizing systematic and common sense approaches to the many judgments involved in designing a study.The Third Edition of Designing Clinical Research (DCR) follows the same path, adding new developments along the way. New material on observational studies includes case-crossover designs, and the use of propensity scores, instrumental variables and Mendelian randomization to control confounding. Reorganized chapters on clinical trials introduce adaptive designs, and those on studying medical tests and on utilizing existing datasets present expanded options that will be attractive to beginning investigators. The chapter on research ethics is extensively updated, the one on data management entirely new (reflecting current approaches to information technology),and a rewritten chapter on study implementation and quality control introduces practicalities of study startup and regulatory issues (‘‘Good Clinical Practices’’). An updated chapter on getting funded brings help for the challenges facing young investigators.

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Handbook of Attachment .. Theory, Research, and Clinical Applications

This comprehensive Handbook provides a landmark review and synthesis of the current state of knowledge about attachment and loss in children and adults. Bringing researchers, clinicians, and students up to date on one of one of the leading theoretical perspectives in contemporary psychology, pre-eminent authorities in the field cover the origins and development of attachment theory, biological perspectives, measurement of attachment across the lifespan, clinical applications, and emerging topics and perspectives.

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Why Clinical Research Can’t Guarantee the Right Medical Answers

It’s Great! Oops, No It Isn’t

Why Clinical Research Can’t Guarantee

the Right Medical Answers

The people are confused because we do not understand the process behind these conflicting results. Our health, and in fact, our very lives are dependent on clinical trials, but we know little about them.

This book explains the issues the public needs to be aware of when it comes to clinical research. It uncovers the problems in medical investigations that can not be overcome no matter how much care and diligence medical researchers bring to a research project. The basic premise that drives the writing is that it is impossible for medical researchers to guarantee that they can get all the right

answers from a single study. No matter how good the investigators are, no matter how well a study is planned, no matter how carefully the plans are executed and no matter how conscientiously the results are analyzed and interpreted – the answer may still be wrong. The deck is stacked against medical researchers and

the public – you – should be skeptical of the results no matter how impressive they seem on the surface.

Do not, however, think that a trial cannot come up with an accurate answer. Many trials have found the correct answer, but there’s never certainty that that will happen. Getting a correct result requires a combination of skill and luck. And furthermore,

the correct result from a single study is almost always a narrow finding.

The drug is proven effective, but its safety still needs to be established. Or perhaps the drug, given in a fixed regimen does not cause kidney damage, but its effect on other systems (heart, liver, lungs etc.) remains unanswered and the results when a different regimen is given may be very different. Note that I emphasize the evaluation of drugs throughout the book because drug testing is the dominant form of medical research and provides many valuable examples of the kind of problems that can be encountered

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Intelligent Drug Development

Clinical research is heavily regulated and involves coordination of numerous pharmaceutical-related disciplines. Each individual trial involves contractual, regulatory, and ethics approval at each site and in each country. Clinical trials have become so complex and government requirements so stringent that researchers often approach trials too cautiously, convinced that the process is bound to be insurmountably complicated and riddled with roadblocks. A step back is needed, an objective examination of the drug development process as a whole, and recommendations made for streamlining the process at all stages.

With Intelligent Drug Development, Michael Tansey systematically addresses the key elements that affect the quality, timeliness, and cost-effectiveness of the drug-development process, and identifies steps that can be adjusted and made more efficient. Tansey uses his own experiences conducting clinical trials to create a guide that provides flexible, adaptable ways of implementing the necessary processes of development. Moreover, the processes described in the book are not dependent either on a particular company structure or on any specific technology; thus, Tansey's approach can be implemented at any company, regardless of size. The book includes specific examples that illustrate some of the ways in which the principles can be applied, as well as suggestions for providing a better context in which the changes can be implemented. The protocols for drug development and clinical research have grown increasingly complex in recent years, making Intelligent Drug Development a needed examination of the pharmaceutical process.

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Key Topics in Clinical Research and Statistics

Key Topics in Clinical Research aims to provide a short, clear, highlighted reference to guide trainees and trainers through research and audit projects, from first idea, through to data collection and statistical analysis, to presentation and publication. This book is also designed to assist trainees in preparing for their specialty examinations by providing comprehensive, concise, easily accessible and easily understandable information on all aspects of clinical research and audit.

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Implementing Research in the Clinical Setting

This practical handbook aims to give the practising nurse and health-care professional the tools to implement research in the clinical setting. There is no intention here of revisiting the deep theoretical issues related to research; rather the book seeks to offer a clear toolkit on how the research might be implemented. Chris Bassett has drawn together the work of six acknowledged experts in this field.

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Epidemiology and Biostatistics An Introduction to Clinical Research

This text provides students and other health professionals with the knowledge necessary to interpret clinical research articles, design clinical studies, and learn essential epidemiological concepts in an expedient and concise manner. Fundamental concepts are presented in a highly succinct format suitable for students with no previous background in epidemiology or statistics.

Drawing on teaching experience and student feedback, the author has created a text that attempts to recreate the perspective of learning epidemiology and biostatistics for the first time. The text serves as a rapid, intensive course in clinical research methods that can be used by students taking the required epidemiology course, residency and fellowship programs for physicians entering the clinical research portion of their training, and clinical research programs in fields such as nursing and nutrition that need an intensive course in clinical research design.

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The Ethical Conduct of Clinical Research Involving Children

In recent decades, advances in biomedical research have helped save or lengthen the lives of children around the world. With improved therapies, child and adolescent mortality rates have decreased significantly in the last half century. Despite these advances, pediatricians and others argue that children have not shared equally with adults in biomedical advances. Even though we want children to benefit from the dramatic and accelerating rate of progress in medical care that has been fueled by scientific research, we do not want to place children at risk of being harmed by participating in clinical studies.

Ethical Conduct of Clinical Research Involving Children considers the necessities and challenges of this type of research and reviews the ethical and legal standards for conducting it. It also considers problems with the interpretation and application of these standards and conduct, concluding that while children should not be excluded from potentially beneficial clinical studies, some research that is ethically permissible for adults is not acceptable for children, who usually do not have the legal capacity or maturity to make informed decisions about research participation. The book looks at the need for appropriate pediatric expertise at all stages of the design, review, and conduct of a research project to effectively implement policies to protect children. It argues persuasively that a robust system for protecting human research participants in general is a necessary foundation for protecting child research participants in particular.

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Common Statistical Methods for Clinical Research with SAS® Examples

Glenn Walker and Jack Shostak's Common Statistical Methods for Clinical Research with SAS Examples, Third Edition, is a thoroughly updated edition of the popular introductory statistics book for clinical researchers. This new edition has been extensively updated to include the use of ODS graphics in numerous examples as well as a new emphasis on PROC MIXED. Straightforward and easy to use as either a text or a reference, the book is full of practical examples from clinical research to illustrate both statistical and SAS methodology. Each example is worked out completely, step by step, from the raw data.

Common Statistical Methods for Clinical Research with SAS Examples, Third Edition, is an applications book with minimal theory. Each section begins with an overview helpful to nonstatisticians and then drills down into details that will be valuable to statistical analysts and programmers. Further details, as well as bonus information and a guide to further reading, are presented in the extensive appendices. This text is a one-source guide for statisticians that documents the use of the tests used most often in clinical research, with assumptions, details, and some tricks--all in one place.

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Conducting GCP- Compliant Clinical Research

Conducting GCP-Compliant Clinical Research Wendy Bohaychuk and Graham Ball Good Clinical Research Practices, UK and Canada The overall aim of this work is to provide a reference book which describes the general framework for conducting GCP-compliant clinical research, particularly pharmaceutical industry clinical research. Wendy Bohaychuk and Graham Ball run a consultancy, GCRP Ltd., which has conducted over 820 GCP audits involving more than 200 companies in the last 10 years. More than 5,000 individuals have been involved in their training courses to help people perform GCP-compliant clinical research. They have authored several books and articles including:

* Standard operating procedures for investigators

* Standard operating procedures for sponsors and CROs

* GCP - an indexed reference

Drawing on their wealth of experience, they have produced this enlightening and practical reference work which fills an educational gap in the understanding of GCP at all levels. Written in concise language simple enough to be accessible to those new in the field, the dozens of real-life stories and detailed case studies at the end of each chapter make the book an invaluable resource for the more experienced, highlighting what can go wrong in a clinical study: A study of prostate cancer in the UK - An investigator brochure was not provided. The company argued that a brochure was unnecessary because the drug was already marketed. Indeed it was - for hypertension! A study of cardiovascular surgery in the UK - The consent dates were changed (by overwriting) to indicate that the patients had provided consent before the study started. The original dates post-dated the start of the study. A study of hypertension in Germany - The investigator brochure predated the study by nine years! Checklists are provided throughout the book to help monitors, auditors and investigators ensure that nothing important is overlooked. The authors present the topic of GCP with remarkable clarity, insight and enthusiasm emphasizing that this code of practice was not designed to make studies more difficult for investigators or more expensive for sponsors and CROs but, in the final analysis, to ensure the safety and well-being of study participants and future patients who will benefit from well-conducted, GCP-

compliant studies.

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Clinical Research Case Studies of Successes and Failures

This book provides insights into how to be a productive clinical researcher via real-life case examples of successful clinical research -- and also clinical research gone awry.  Through these examples of success and failure, the book develops a blueprint for building a career in clinical research.

 Future medical practice depends on the quality of the clinical trials to which drugs, devices, and treatment procedures are subjected today.  However, clinical trials are not easy to do, and many physicians and health care providers who attempt clinical research struggle in this endeavor, primarily because of lack of instruction. Clinical Research aims to fill the gap between training and research through case studies of a long-time clinical researcher’s rich and varied experiences.

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Clinical Research Manual: Practical Tools and Templates for Managing Clinical Research

Clinical Research Manual: Practical Tools and Templates for Managing Clinical Research is the "must-have" book for anyone working in the day-to-day operations of a research study or clinical trial. Filled with tools, techniques, and templates, this manual offers clinical researchers, principal investigators, and research coordinators the foundation they need to successfully organize complex trials.

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Clinical Research Coordinator Handbook: Gcp Tools and Techniques

This revised edition of a bestseller provides a logical, step-by-step guide to testing new drugs and treatment modalities in compliance with the latest FDA regulations. With current forms, ICH GCP information, FDA regulations, and other references, it shows readers how to manage a clinical research study effectively and efficiently.

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An Introduction to Clinical Research

This practical book is written specifically for junior doctors by a team of highly experienced authors, as an introductory guide to clinical research. It covers all areas that a junior doctor needs to consider, including funding, study design, ethics, data analysis, disseminating findings, and furthering one's research career. It presents a balance view of clinical research and is written by authors actively involved in clinical research both at the 'coal-face' and at a more supervisory level. Research can be a difficult process and it is essential to make sure that the project is set up in the correct way in order to get verifiable results. This easy-to-read guide is available to help junior doctors develop a good study design and present evidence of a sound academic practice, which will make obtaining funding more likely and be time-efficient. Getting started early in research and developing a solid, gradual understanding of clinical research through using this approachable book will be of huge benefit to junior doctors and their discipline.

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A Guide to Clinical Drug Research

Following the success of the first edition, published in 1995, this fully rewritten A Guide to Clinical Drug Research - Second Edition has been adapted to the most recent guidelines and developments in the field. It continues to provide a wealth of practical advice, ranging from the conception of an idea, planning a study and writing a protocol, through to the conduct of a study, data collection and analysis, and publication. It tells investigators what information they should expect sponsoring companies to provide, particularly when there is only limited information available about a new drug. It also explains what the company can expect of investigators, including the requirements of `good clinical practice'. Unlike other currently available texts on clinical trials and pharmaceutical medicine, A Guide to Clinical Drug Research concentrates on the needs of the practising clinician and research team. It is not restricted to drug investigation, and is relevant to all those involved in clinical research in a variety of settings. 

Audience: Required reading for clinical researchers and others involved as investigators in a drug project, often sponsored by a pharmacuetical company, plus agents of the sponsoring companies themselves.

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A Practical Guide to Quality Management in Clinical Trial Research

Setting up a GXP environment where none existed previously is a very daunting task. Getting staff to write down what they do for every task is a correspondingly difficult and time-consuming exercise. Examining how to maintain quality control in clinical trial research, A Practical Guide to Quality Management in Clinical Trial Research provides a cornerstone of knowledge for establishing a quality system that complies with the relevant regulations. There are many books available that cover how to interpret regulations. Going a step or two further, this book provides practical advice that is useful on a daily basis.

The book contains information for various standards including GLPs, GCPs, and GMPs. It gives detailed explanations of how to prepare, update, and maintain SOPs and includes advice on training and development of personnel. Drawing directly on his years of experience, the author delineates a from-the-trenches methodology that creates a value-added quality management system from a business perspective. He provides a solid foundation as well as tips and techniques for establishing a quality system that will comply with all the relevant regulations. The author's integrated approach and anecdotal style turns technically accurate information into easy reading. The book arms you with tools and concepts that you can use to go beyond regulatory compliance and move into the realm of business quality improvement.

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A Clinical Trials Manual from the Duke Clinical Research Institute

"The publication of the second edition of this manual comes at an important juncture in the history of clinical research. As advances in information technology make it possible to link individuals and groups in diverse locations in jointly seeking the answers to pressing global health problems, it is critically important to remain vigilant about moral and ethical safeguards for every patient enrolled in a trial. Those who study this manual will be well aware of how to ensure patient safety along with fiscal responsibility, trial efficiency, and research integrity."

-Robert Harrington, Professor of Medicine, Director, Duke Clinical Research Institute, Durham, North Carolina, USA

The Duke Clinical Research Institute (DCRI) is one of the world's leading academic clinical research organizations; its mission is to develop and share knowledge that improves the care of patients around the world through innovative clinical research. This concise handbook provides a practical "nuts and bolts" approach to the process of conducting clinical trials, identifying methods and techniques that can be replicated at other institutions and medical practices.

Designed for investigators, research coordinators, CRO personnel, students, and others who have a desire to learn about clinical trials, this manual begins with an overview of the historical framework of clinical research, and leads the reader through a discussion of safety concerns and resulting regulations. Topics include Good Clinical Practice, informed consent, management of subject safety and data, as well as monitoring and reporting adverse events.

Updated to reflect recent regulatory and clinical developments, the manual reviews the conduct of clinical trials research in an increasingly global context. This new edition has been further expanded to include:

• In-depth information on conducting clinical trials of medical devices and biologics
• The role and responsibilities of Institutional Review Boards, and
• Recent developments regarding subject privacy concerns and regulations.

Ethical documents such as the Belmont Report and the Declaration of Helsinki are reviewed in relation to all aspects of clinical research, with a discussion of how researchers should apply the principles outlined in these important documents. This graphically appealing and eminently readable manual also provides sample forms and worksheets to facilitate data management and regulatory record retention; these can be modified and adapted for use at investigative sites.

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European Textbook on Ethics in Research

This textbook results from a contract awarded by the European Commission to the Centre for Professional Ethics at Keele University (also known as PEAK). The tender for the contract was written by Jonathan Hughes and Mark Sheehan, and incorporated a provisional outline for the textbook based on PEAK’s experience as a leading provider of training for research ethics committees in the health and university sectors in the UK and Ireland since 2003. In writing the textbook we have been fortunate in being able to draw upon PEAK’s extensive library of teaching resources, developed for its research ethics committee training programmes and its distance learning master’s degree in research ethics. We are grateful to the past and present members of staff who have produced these materials and to the Centre itself for permission to incorporate them into the textbook. The textbook is edited by Jonathan Hughes, who also wrote the Introduction and Chapters 5 and 6. Authorship of the other chapters is as follows (all members of PEAK except where indicated). Chapter 1: David Hunter; Chapter 2: Stephen Wilkinson; Chapters 3 and 4: Anthony Wrigley; Chapters 7 and 8: Mark Sheehan (formerly a member of PEAK but now at Oxford University and the Oxford NIHR Biomedical Research Centre). Allison Ross contributed to the planning of the textbook and Monique Jonas made contributions to the content and editing of several chapters. We also received valuable input from outside Keele. A draft syllabus of the book, incorporating the case studies, was sent out for consultation to a variety of academic experts and research ethics practitioners from across Europe. We are grateful to the individuals and organisations that took the trouble to respond, and we have endeavoured to incorporate their suggestions. Lino Paula, the Scientific Officer at the European Commission responsible for this project, helped to organise the consultation and provided valuable suggestions at various stages in the planning and writing process. Roger Burns, Michelle Cunningham, Celia Diver-Hall and Anne Evans commented on the final draft of the textbook from the perspective of students recently enrolled on courses in professional or research ethics. Andrew Astley commented from the perspective of a lay member of an ethical review panel at Keele. Beverley Sykes provided professional copy editing of the final draft.

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DESIGN AND ANALYSIS OF CLINICAL TRIALS....Concepts and Methodologies

Clinical trials are scientific investigations that examine and evaluate safety and efficacy of drug therapies in human subjects. Biostatistics has been recognized and extensively employed as an indispensable tool for planning, conduct, and interpretation of clinical trials. In clinical research and development, the bio-statistician plays an important role that contributes toward the success of the trial. An open and effective communication among clinician, biostatistician, and other related clinical scientists will result in a successful clinical trial. The mutual communication, however, is a two-way street: not only (1) the biostatistician must effectively deliver statistical concepts and methodologies to his/her colleagues but also (2) the clinician must communicate thoroughly clinical and scientific principles embedded in clinical research to the biostatistician. The biostatistician can then formulate these clinical and scientific principles into valid statistical hypotheses, models, and methodologies for data analyses. The integrity, quality, and success of a clinical trial depend on the interaction, mutual respect, and understanding among the clinician, the biostatistician, and other clinical scientists. There are many books on clinical trials already on the market. These books, however, emphasize either statistical or clinical aspects. None of these books provides a balanced view of statistical concepts and clinical issues. Therefore the purpose of this book is not only to fill the gap between clinical and statistical disciplines but also to provide a comprehensive and unified presentation of clinical and scientific issues, statistical concepts, and methodologies. Moreover this book focuses on the interactions among clinicians, biostatisticians, and other clinical scientists that often occur during the various phases of clinical research and development. This book is intended to give a well-balanced overview of current and emerging clinical issues and newly developed statistical methodologies. Although this book is written from a viewpoint of pharmaceutical research and development, the principles and concepts presented in this book can be applied to nonbiopharmaceutical settings.

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SAS® Programming in the Pharmaceutical Industry

This book was written for the entry- to intermediate-level SAS programmer who helps with the analysis and reporting of clinical trial data in the pharmaceutical industry. The industry may call this individual a “SAS programmer,” “clinical SAS programmer,” “statistical/stats programmer,” “programmer/analyst,” or any of a host of other names. In this book we call this individual a statistical programmer. Although this book may prove useful to clinical trial statisticians, it is aimed more at the statistical programmer who assists the lead trial statistician in producing the large amount of reporting required. This book assumes that the reader has no prior knowledge of clinical trials and some knowledge of SAS programming. Most statistical programmers who end up working in clinical trial analysis happen upon the field by accident. This is primarily because historically there have been few if any formal training programs for clinical trial SAS programming. As a result, most statistical programmers have to learn about clinical trial analysis and reporting on the job. I thought it would be beneficial to have a resource for the junior statistical programmer that brings together in one volume much of the knowledge required to do clinical trial reporting. This book is organized chronologically according to the statistical programmer’s workflow. There is an introductory chapter that defines the working environment and sets the basic ground rules for the job. Then, there are chapters on importing data and massaging data into analysis data sets. Producing clinical trial report output is covered in the chapters on tables, listings, and graphs. Finally, there is a chapter on exporting data, followed by a discussion of the future for statistical programmers and a closing chapter on further resources. The examples in this book focus primarily on the tools within SAS/GRAPH, SAS/STAT, and Base SAS, including the SAS macro language and PROC SQL. The examples were developed using SAS 9.1.3, but the vast majority of the examples will run with other versions of SAS as well. Please note that the data that drive the examples in this book are obtained through INPUT statements with DATALINES data. This is done only for illustrative purposes and does not mean that you should expect to obtain your clinical data in this fashion.

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