Human Experimentation - Cleophas, Ton J.

Professor Zwinderman is one of the Principle Investigators of the Academic Medical Center Amsterdam, and his research is concerned with developing statistical methods for new research designs in biomedical science, particularly integrating omics data, like genomics, proteomics, metabolomics, and analysis tools based on parallel computing and the use of cluster computers and grid computing.

Professor Cleophas is a member of the Academic Committee of the European College of Pharmaceutical Medicine, that provides, on behalf of 22 European Universities, the Master-ship trainings Pharmaceutical Medicine and Medicines Development.

From their expertise theyshould be able to make adequate selections of modern methods for clinical data analysis for the benefit of physicians, students, and investigators. The authors have been working and publishing together for 18 years, and their research can be characterized as a continued effort to demonstrate that clinical data analysis is not mathematics but rather a discipline at the interface of biology and mathematics.

The authors as professors and teachers in statistics at universities in The Netherlands and France for the most part of their lives, are concerned, that their students find regression-analyses harder than any other methodology in statistics. This is serious, because almost all of the novel methodologies in current data mining and data analysis include elements of regression-analysis, and they do hope that the current production Regression Analysis for Starters and 2nd Levelers will be a helpful companion for the purpose.

Statistics applied to clinical studies 5th edition, 2012, ...

Sommaire:
1 Placebos.- 1.1 Introduction.- 1.2 Ethical problems with placebo-controlled trials.- 1.3 Benefits of placebo-controlled trials.- 1.4 Technical problems with placebo-controlled trials.- 1.5 Conclusions.- 2 Fundamental Issues of Choosing the Right Type of Trials.- 2.1 Introduction.- 2.2 Ethical problems.- 2.3 Costs.- 2.4 Sample size.- 2.5 Between-subject variability of symptoms.- 2.6 Physical carryover effects.- 2.7 Time effects.- 2.8 Correlation between treatment modalities.- 2.9 Conclusions and examples.- 3 Lack of Real Science of Symptom-Based Care.- 3.1 Introduction.- 3.2 Methods.- 3.3 Study selection and data extraction.- 3.4 Data synthesis.- 3.5 Discussion.- 4 Carryover Effects in Clinical Research.- 4.1 Introduction.- 4.2 Dose response and dose titration studies.- 4.3 Studies with duplicate standard deviations.- 4.4 Open evaluations studies.- 4.5 Cross-over studies.- 4.6 Self-controlled Studies.- 4.7 Parallel-group studies.- 4.8 Studies with subjective variables.- 4.9 Discussion.- 5 Criticism of Negative Studies due to Negative Correlations.- 5.1 Introduction.- 5.2 Levels of correlation and sensitivity of testing.- 5.3 A simple test to check a posteriori whether the cause of a negative result is its level of correlation.- 5.4 Review of published crossover studies with a presumably negative correlation.- 5.5 Review of published crossover studies with a presumably positive correlation.- 5.6 Conclusions and recommendations.- 5.7 Conclusions.- 6 Between-Group Disparities in Drug Response.- 6.1 Introduction.- 6.2 Statistical model.- 6.3 Hypothetical examples, power analysis.- 6.4 Discussion.- 7 Specific Problems with Trials of Chronic Diseases.- 7.1 Introduction.- 7.2 Published clinical trials.- 7.3 Strengths and weaknesses of the two designs.- 7.4 Stage of study and the type of trial.- 7.5 More recent statistical papers on the subject.- 7.6 Conclusions.- 8 Clinical Trials with New Endpoints.- 8.1 Introduction.- 8.2 Subjective endpoints.- 8.3 New ethical priorities.- 8.4 Human touch rather than scientific rigor.- 8.5 Little emphasis on informed consent.- 8.6 Self-controlled rather than parallel-group designs.- 8.7 Conclusions.- 9 Linear Scale Assessment of Relevant Domains of Quality of Life - an example.- 9.1 Introduction.- 9.2 Patients and methods.- 9.3 Results.- 9.4 Discussion.- 10 Item Response Modeling and Quality of Life.- 10.1 Introduction.- 10.2 Methods.- 10.3 Results.- 10.4 Discussion.- 11 Is Selective Reporting of Well-Designed Research Unethical as Well as Unscientific ?.- 11.1 Introduction.- 11.2 Arguments against reporting negative studies.- 11.3 Arguments in favor of reporting negative studies.- 11.4 How progress of science was made in the past.- 11.5 Today the progress of science is faster, new rules are required.- 11.6 Suggestions for a balanced approach to the problem of selective reporting.- 11.7 Conclusions.- 12 Informed Consent Under Scrutiny, Suggestions for Improvement.- 12.1 Introduction.- 12.2 Ethical difficulties with the informed consent principle.- 12.3 Ethical difficulties with the informed consent process.- 12.4 Example of a flawed consent information form of a double-blind parallel-group study.- 12.5 Suggestions for improvement of the informed consent procedure.- 12.6 Conclusion.