E9 Statistical Principles for Clinical Trial

E9 Statistical Principles for Clinical Trials, found at http //www.fda.gov/cder/guidance/ICH E9-fnl.PDF. 

Statistical thinking and practice is very much determined by the regulatory guidelines that are in place. Primarily it is ICH E9 Statistical Principles for Clinical Trials , published in 1998, which sets down the broad framework within which we operate. In 2001 we saw the publication of ICH ElO Choice of Control Group which contained advice on the appropriate choice of concurrent control group and in particular first introduced the concept of assay sensitivity (see Section 12.5) in active control, non-inferiority trials. 

International Conference on Harmonisation. Guidance for Industry E9. Statistical Principles for Clinical Trials. CDER, FDA, Rockville, MD, 1998. 

Given the level of research activity devoted to identification of influential observations, considerably less effort has been devoted to what to do about them. Under guidelines (E9 Statistical Principles for Clinical Trials) developed by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (1997), more commonly called ICH, several principles for dealing with outliers or influential observations are presented. First, data analysis should be defined prior to analyzing the data, preferable before data collection even begins. The data analysis plan should specify in detail how outliers or influential observations will be handled. Second, in the absence of a plan for handling outliers or influential observations, the analyst should do two analyses, one with and the other without the points in question, and the differences between the results should be presented in the discussion of the results. Lastly, identification of outliers should be based on statistical, as well as scientific rationale, and that the context of the data point should dictate how to deal with it. 

ICH. International Conference on Harmonisation. An international forum for regulatory authorities in the European Union, Japan and the United States established in 1990. The ICH has issued more than 60 documents of regulatory guidance divided into the major areas of Quality (Q), Safety (S), Efficacy (E) and Multidisciplinary (M). Many of these are relevant to this book but the most relevant is ICH E9 Statistical Principles for Clinical Trials. 

All chapters have been brought up to date in the new edition and in particular, there is extensive reference to various guidelines of the International Conference of Harmonization that have been issued since the first edition, in particular ICH E9, Statistical Principles for Clinical Trials. A new chapter on pharmaco-genetics has been added. For the reader in possession of a first edition who wishes to know whether to splash out on a second, Figure P.l may be helpful. (This is partly so that I can underline the fact that nothing in life, not even an author s preface, should be exempt from statistics ) This compares the two editions chapter by chapter in terms of their length in thousands of words. 

ICH E9 (1998) Note for Guidance on Statistical Principles for Clinical Trials ... 

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