Fundamentals of Clinical Research: Bridging Medicine, Statistics and Operations

ISBN-13: 9788847056336 / Angielski / Miękka / 2014 / 343 str.

Antonella Bacchieri;Giovanni Della Cioppa

Opis

Statistical methodology is an essential component of clinical (and biological) - search. Therefore it is not surprising that many textbooks aiming at explaining statistical methods to researchers have been published and continue to appear in print. The complexity of the basic issue, that of communication between st- isticians and researchers, is illustrated and discussed very well by the authors of this book in their Introduction. Thus it would be of no benefit to dwell further on this theme and on the difficulty of producing truly effective material. I prefer to start from a personal episode. Way back in 1959, a freshman of the faculty of Statistical Sciences, I found by chance on a stand, the book Metodi statistici ad uso dei ricercatori, which was the Italian translation of the famous book by RA Fisher. The textbook for the first course of statistics used that year at of our University had left me perplexed. A student like myself, with a good high school scientific education, was fascinated by the wealth of real life ex- ples, but was unable to reconstruct the thread of logical-mathematical reas- ing, especially the inductive one. The unexpected access to Fisher s legendary book raised my hopes that I could finally get to the heart of the matter."

Recenzje

From the reviews:

"The first three chapters of the book provide important foundational information. ...Chapters 4, 6, and 7 are the stars of this book. The authors lay out in great detail the complex process of arriving at a measure of treatment effect. We statisticians are so used to having this handed to us that we never think about how important this process is. The authors also provide pragmatic advice about whether to select your sample to be mildly ill or seriously ill, or whether you should choose healthy volunteers instead." Steve Simon, Journal of Biopharmaceutical Statistics, Issue 2, 2008

"Main aim of this book is to explain the three pillars of clinical research: medicine, statistics and logistics in an easily digestible manner. ... A very lucid and well-structured account of the basic statistical and epidemiological concepts is definitely a great plus point of this book ... . I have truly enjoyed reading this book and it gives a refreshing and focused outline of the clinical research. I would recommend all clinicians who aspire to be/are involved in clinical research to give it an audience." (Faisel Yunus, Journal of Applied Statistics, Vol. 35 (2), 2008)

"Readership: ... the clinical researcher who wants an intelligent discussion on the (mainly) statistical aspects of clinical research. It would make a useful background reading for a course in clinical trials. ... The book is well written. ... is essentially an extended essay on the application of statistical inference in clinical research." (M. J. Campbell, International Statistical Review, Vol. 75 (3), 2007)

"A comprehensive introductory text that addresses statistical methods and operational issues in the conduct of clinical research. ... The authors avoid overuse of mathematical formulas and carefully balance practical and theoretical aspects of clinical research. Format and writing clarity are good, with numerous examples used to illustrate concepts throughout the text. ... Recommended Readership: Doctoral and postdoctoral trainees and junior or research inexperienced clinical researchers and scientists." (Paul V. Targonslci, Mayo Clinic Proceedings, Vol. 82 (11), November, 2007)

"The text is directed toward physicians conducting clinical trials research and statisticians consulting on clinical trials. ... I recommend it for physicians, statisticians, and technical personnel with a novice knowledge level of clinical trials. At the same time it could be used as a text for an introductory graduate level class in clinical trials. To those entering the field of clinical trials I wholeheartedly recommend Fundamentals of Clinical Research ... as it provides a foundation pertinent to a variety of aspects of clinical trials research." (Gregory E. Gilbert, The American Statistician, Vol. 63 (1), February, 2009)

"The authors' book on methods and issues in clinical research is directed at biomedical researchers as well as statisticians. ... it addresses the integration of medical and statistical components of clinical research in order to create a logical flow of reasoning understandable for both the medical/biological and the statistical expert. ... The whole book is written in a convenient, comprehensible style ... and is therefore useful also for readers having more advanced knowledge and experience in the field of clinical trials." (Lutz Edler, Zentralblatt MATH, Vol. 1210, 2011)

Spis treści

1. Variability of Biological Phenomena and Measurement Errors 1.1. Phenotypic Variability 1.2. Temporal Variability. 1.3. Measurement - Related Variability 1.3.1. The Measurement 1.3.2. Measurement Errors 1.4. Variability of Diagnostic Tests Summary 2. Distinctive Aspects of a Biomedical Study. Observational and Experimental Studies 2.1. Distinctive Features of Biomedical Studies 2.2. The Study Protocol 2.3. Observational Studies 2.4. Experimental Studies Summary 3. Observational Studies 3.1. Basic Designs of Observational Studies 3.1.1. Prospective or Cohort Studies 3.1.2. Retrospective Studies or Control Cases 3.1.3. Sample Size 3.2. Bias and Confounding 3.2.1. Control of Bias in Epidemiology 3.2.2. Control of the Phenomenon of Confounding | 3.3. Advantages and Disadvantages of the Different Types of Observational Studies Summary 4 Defining the Treatment Effect 4.1. From the Single Measurement to the Signal 4.2. Identification and Quantification of the End-Points (Individual Subject Level) 4.2.1. Methodological Characteristics of the End-Point 4.2.2 Discriminating Between Primary and Secondary End-Points and Between Efficacy and Safety/Tolerability End-Points 4.3. Identification and Quantification of the Signals (Group Level) 4.4. Statistical Considerations 4.5. Practical, Regulatory, Marketing and Pharmaco-Economic Considerations 4.6. Selection and Characterization of the Primary End-Point and Signal: an Example 4.6.1. Stage One: Define the Main Therapeutic Level 4.6.2. Stage Two: Define the Primary End-Point (Individual Patient Level) 4.6.3. Stages Three and Four: Define the Group Indicator, the Signal, and the Threshold of Clinical Relevance (Treatment Group and Study Levels) 4.7. More Than One Question in the Same Study: the Problem of Multiple Statistical Tests 4.8. Validation of Measurement Scales 4.9. Special Types of End-Points Summary 5. Probability, Inference and Decision Making 5.1. Probability 5.1.1 Definitions 5.1.2. Probability Distribution and Probability Density Function 5.1.3. Normal or Gaussian Distribution 5.2. Basic Concepts of Inference 5.2.1. Hypothesis Testing and Statistical Formulation of the Medical Question 5.2.2. Statistical Estimation as the Tool for Evaluation of Clinical Relevance 5.3. Statistical Inference in the Frequentist and the Bayesian Approaches 5.4. Two Digressions: Measures of Variability and Likelihood Function 5.4.1. Measures of Variability 5.4.2. Likelihood Function 5.5. Frequentist (Classical) Analysis of a Clinical Trial 5.5.1. Hypothesis Testing: the Frequentist Solution 5.5.2. Estimation of the Effect: the Frequentist Solution 5.6. Bayesian Analysis of a Clinical Trial 5.6.1. Hypothesis Testing: the Bayesian Solution 5.6.2. Estimation of the Effect: the Bayesian Solution 5.7. Some Additional Considerations on the Frequentist and Bayesian Approaches 5.8. Parametric and Non-Parametric Inference 5.9. Statistical Decision Making in the Medical Field 5.10. Evidence-Based Medicine Summary 6. The Choice of the Sample 6.1. Which Subjects Should Form the Sample? 6.1.1. Characteristics of the Patients to be Enrolled in the Study 6.1.2. Mechanism of Subject Selection 6.2. How Many Subjects Should Form the Sample? 6.2.1. Statistical Considerations 6.2.2. Medical and Practical Aspects Summary 7. The Choice of Treatments 7.1. Study Treatments 7.1.1. How Many Treatments 7.1.2. What Treatments 7.1.3. Blinding of the Study Treatments 7.1.4. Packaging and Logistics 7.2. Concomitant Treatments Summary 8. Experimental Design: Fallacy of 'Before-After' Compa

Blurb

The scope of clinical research is to evaluate the effect of a treatment on the evolution of a disease in the human species.The treatment can be pharmacological, surgical, psychological/behavioral or organizational/logistic. The disease, intended as an impairment of a state of well-being or a condition capable of provoking such impairment over time, can be universally accepted as such (e.g. a cancer or a bone fracture) or perceived as such only by limited groups of individuals in a given cultural context (e.g. hair loss or weight gain). The course of the disease that ones wishes to change can be the one with no intervention or, more frequently, the one observed with the available treatment. The evaluation of the effect of a treatment on the course of a disease is a lengthy process, which progresses in increasingly complex stages.

A detailed coverage of the logistic, administrative and legal aspects of clinical research is outside the scope of this book. However, throughout the book we keep reminding the reader of these aspects because, as already mentioned, we firmly believe they have a crucial role in determining the success of a study. The history of clinical research is paved with relics of studies started with great pomp, riding great ideas and great hopes, which drowned miserably because of inadequate logistical preparation. In our experience, the excessive complexity of a clinical trial is the single most frequent cause of failure: the study is perfect on paper, but impossible to implement by patients and staff alike. The distance between the principal investigators and the reality of clinical research in its day-to-day practice is often the main cause of such disasters. We warmly encourage everyone involved in clinical research to get involved in the logistics of a study, learning from colleagues responsible for its practical conduct (clinical research associates, data managers, etc.) and to take part, in person, in the practical implementation of a trial before attempting to design a study protocol.

The book ends with a brief description of the drug development process and to the phases of clinical development.

The authors