Design of Experiments and Advanced Statistical Techniques in Clinical Research

ISBN-13: 9789811582127 / Angielski / Miękka / 2021

Basavarajaiah D. M.;Bhamidipati Narasimha Murthy

Opis

Recent Statistical techniques are one of the basal evidence for clinical research, a pivotal in handling new clinical research and in evaluating and applying prior research. This book explores various choices of statistical tools and mechanisms, analyses of the associations among different clinical attributes. It uses advanced statistical methods to describe real clinical data sets, when the clinical processes being examined are still in the process. This book also discusses distinct methods for building predictive and probability distribution models in clinical situations and ways to assess the stability of these models and other quantitative conclusions drawn by realistic experimental data sets. Design of experiments and recent posthoc tests have been used in comparing treatment effects and precision of the experimentation. This book also facilitates clinicians towards understanding statistics and enabling them to follow and evaluate the real empirical studies (formulation of randomized control trial) that pledge insight evidence base for clinical practices. This book will be a useful resource for clinicians, postgraduates scholars in medicines, clinical research beginners and academicians to nurture high-level statistical tools with extensive scope.

Spis treści

1 Design of Clinical Research and its Practical approach……………..............................................................

1.1 Introduction……………………………………………………………..

1.2 Statistical Historical Perspectives of Clinical trail…………………….. 

1.2.1 Global mile stone………………………………………………….

1.2.2 Indian mile stone…………………………………………………

1.3 Clinical research……………………………………………………

1.3.1 Intervention……………………………………………………….

1.3.2 Non intervention…………………………………………………

1.4 Types of clinical research…………………………………………….

1.4.1 Patient oriented research…………………………………………

1.4.2 Epidemiological and behavioral studies………………………… 

1.4.3 Out come and health related services research………………….. 

1.5 Risk in clinical research…………………………………………………

1.6 Clinical trial…………………………………………………………….

1.6.1 Treatment trial……………………………………………………

1.6.2 Prevention trial…………………………………………………..

1.6.3 Quality of life trial………………………………………………

1.6.4 Diagnostic trial …………………………………………………..

1.7 Glossary………………………………………………………………..

1.8 Brief concept of study design………………………………………….

1.9 Experimental study…………………………………………………….

1.9.1 Randomized controlled trail (RCT)………………………………

1.9.2 Non Randamized controlled trail (RCT)………………………….

1.10 Randomization study………………………………………………….

1.10.1 Salient Properties of Randamizatin…………………………….

1.11 Non randomization …………………………………………………..

1.11.1 Cohort study………………………………………………….

1.11.2 Selection of study subjects………………………………………

1.11.3 Carrying out research on special populations…………………..

1.11.4 Justice………………………………………………………….

1.11.5 Obtaining data sets on exposure……………………………….

1.11.6 Selection of comparison ………………………………………..

1.11.7 Follow up record……………………………………………….

1.11.8Compilation and inference………………………………………

1.11.9 Strength of cohort study ………………………………………

1.11.10 Weakness of Cohort study design……………………………

1.12 Cross sectional study…………………………………………………..

1.13 Longitudinal study……………………………………………………

1.14 Prospective study…………………………………………………….

1.15 Retrospective study: case control……………………………………..

1.16 Case control study……………………………………………………..

1.17 Different phases of clinical trial……………………………………..

1.18   Study population……………………………………………………..

1.19   Statistical issues and methods………………………………………..

1.20 Application of multinomial distribution in clinical trial……………….

1.21 Gehans’s Two stage design…………………………………………….

1.22 Two stage Simon’s Experimental design……………………………….

1.23   Randomized clinical trial…………………………………………….

1.23.1 Simple randomization ………………………………………..

1.23.2 Block randomization ………………………………………..

1.23.4 Minimization method stratification……………………………..

1.24 Pragmatic clinical trails (PCTs)……………………………………….

1.24.1 Limitation……………………………………………………..

1.24.2Statistical implications of pragmatic design……………………

1.25 Cluster RCTs design……………………………………………………

1.26 Cross over design……………………………………………………….

1.26.1 Limitations……………………………………………………….

1.27 Delayed start design……………………………………………………

1.27.1 Indicators………………………………………………………. 

12.27.2 Merits………………………………………………………….

1.27.3 Demerits………………………………………………………..

1.28 Randamized with drawl design…………………………………………

1.28.1 Merits ………………………………………………………….

1.28.2 Demerits…………………………………………………………

1.29 Adaptive design………………………………………………………

1.29.1 Merits ………………………………………………………….

1.30 Non experimental methods……………………………………………

1.31 New user design……………………………………………………….

1.32 Glossary………………………………………………………………..

1.32.1 Random variable…………………………………………………

1.32.2 Conditional expectation…………………………………………

1.32.3 Conditional variance……………………………………………..

2 Design of Experiment approach to clinical research……

2.1 Introduction…………………………………………………………….

2.1.1 Replication……………………………………………………….

2.1.2 Randomization…………………………………………………….

2.1.3 Control of error…………………………………………………

2.2 Design on single factor clinical experiments…………………………..

2.3 Complete  randomized design ………………………………………

2.3.1Randomization…………………………………………………..

2.3.2  Analytical method………………………………………………

2.3.3  Analysis of variance (ANOVA)……………………………….

2.4 Randomized complete block design …………………………………

2.4.1 Blocking techniques……………………………………………

2.4.2 Randomization and lay out……………………………………

2.4.3 Analytical method……………………………………………….

2.4.4 Analysis of variance (ANOVA)…………………………………..

2.5 Latin square design(LSD)……………………………………………

2.5.1  Randomization and lay out………………………………………. 

2.5.2  Analytical method………………………………………………..

2.6 Cross over design (COD) ……………………………………………

2.6.1  Data collection and documentation……………………………..

2.6.2 Masking or blinding……………………………………………….

2.7 2.7  Ethical issues………………………………………………………

2.8 2.8  Sampling techniques……………………………………………

3 Statistical Perspective approach to Selection of Sample in Clinical research…………………………………………

3.1 Introduction-Statistical Dealing with Success of Good Research …….

3.2 Research Perspectives in new Horizon……………………………

3.3 Statistical thinking on thematic research area…………………………..

3.4 Methods -Formulation and frame work of Research Project…………

3.5 Sample size Determination …………………………………………..

3.6 Results………………………………………………………………….

3.7 Merits of sample size determination……………………………………

3.8 Demerits of sample size determination………………………………..

3.9 Level of precision……………………………………………………

3.10 The Confidence Level………………………………………………..

3.11 Using a sample Size of a Similar Study……………………………..

3.12 Degree of Variability……………………………………………….

3.13 Discussion…………………………………………………………..

3.1 Conclusion ……………………………………………………………

3.15 Summary ………………………………………………………………

Reference………………………………………………………………

4 Statistical Models approach to ARV drugs ………………………..

4.1 Introduction…………………………………………………………….

4.2 Model description……………………………………………………….

4.3 Demographic features of HIV infected women……………………….

4.4 Intrauterine and intrapartum transmission ……………………………

4.5 Transmission probability at or before birth, in the absence of ARV-Prophylaxis……………………………………………………………

4.6 Neural network modelling in HIV/AIDS …………………………….

4.7 Application of neural net work in medical science…………………….

4.8 4.8 Equation- survival analysis –Model construct…………………….

4.9 Model -Proof…………………………………………………………..

4.10 Hierarchical neural nets for survival analysis………………………….

4.11 Non hierarchical neural nets for Survival analysis…………………….

4.12 Salient findings of neural net work model fitting……………………..

4.13 Application of the neural net work in HIV or Medical research ……….

4.14   Modeling on assessment of quality of life of patients…………………

4.15 Model formulation ……………………………………………………

4.16 principle component analysis…………………………………………

4.17 Model discussion………………………………………………………

4.18 Summary…………………………………………………………….

5 Statistical methods for clinical research……………………………..

5.1 Bio equilance trail………………………………………………………

5.2 Equivalence testing, a new gold standard………………………………

5.3 Comparing two response rates…………………………………………

5.4 Characteristics of normal distribution………………………………….

5.5 Log normal distribution………………………………………………..

6 Survival analysis……………………………………………………..

6.1 Introduction…………………………………………………………….

6.2 Model description……………………………………………………

6.3 Survival analysis………………………………………………………

6.4 Survival function……………………………………………………….

6.5 Concept of the model …………………………………………………

6.5.1 Survival function……………………………………………….

6.5.2 Estimation of  s(t)……………………………………………….

6.5.3  Probability density function…………………………………….

6.6 Hazard Function(Hz)…………………………………………………..

6.7 Hazard rate

 6.7.1 Survivability of different CD4 category with HAART duration…

 6.7.2 Kaplan-Meier survival curve …………………………………

6.8 Exponential distribution……………………………………..

5.18 Gompertz –Makeham distribution model…………………..

6.9 Censoring and life table methods………………………….

6.10 Kaplan Meir analysis………………………………………

6.11 Estimation with censored data …………………………….

6.12 Non informative censoring…………………………………………….

6.13 Mantel-Haenszel test………………………………………………….

6.14 K-Sample Mantel-Haenszel test………………………………………..

7 Image processing modeling on radiographic features…..

7.10 Introduction…………………………………………………………………….

7.11 Analog image processing…………………………………………………………

7.12 Digital image processing ………………………………………………

7.13 Application of digital image processing……………………………….

7.14 Different stages of digital image processing …………………………

7.15 Signal………………………………………………………………….

7.16 Relationship……………………………………………………………

7.17 How a digital image is formed……………………………………………………..

7.18 Overlapping fields-Machine computer vision ………………………..

7.19 Computer graphics……………………………………………………..

7.20 Artificial intelligence…………………………………………………

7.21 Signal processing……………………………………………………

7.22 Signals……………………………………………………………

7.23 Analog signal…………………………………………………………

7.24 Human voice…………………………………………………………….

7.25 Digital signal……………………………………………………….

7.26 System………………………………………………………………… 

7.27 Sampling……………………………………………..

7.28 Quantization………………………………………………………….

7.29 Application of digital image processing…………………………….

7.30 Image sharpening and restoration …………………………………

7.31 UV imaging…………………………………………………………………….

7.32 Transmission and encoding…………………………………………..

7.33 Machine /Robot vision……………………………………………….

7.34 Hurdle detection……………………………………………………..

7.35 Line follower robot…………………………………………………………..

7.36 Color processing ………………………………………………………

7.37 Pattern recognition…………………………………………………….

7.38 Video processing…………………………………………………….

7.39 Modeling on image processing ………………………………………..

7.40 Camera pixels…………………………………………………………………

7.41 Oversampling……………………………………………………………….

7.42 Zooming……………………………………………………………………….

7.43 Pixel…………………………………………………………………………

7.44 Resolution………………………………………………………………………

7.45 Megapixels  …………………………………………

7.46 Advantage………………………………………………………………

7.47 Kernel regression model for image processing…………….

7.48 Advanced model of image processing ………………………

8 Factors affecting drug response……………………………

9 Pharmokinitic modelling (PK)……………………………..

10 Genetic variants of drug potency…………………………..

11 Application of posthoc test for comparison of potency of drug trail……………………………………………………

12 Advanced design of experiment in clinical trail………….

13 Data base management of clinical research………………

14 Ethical perspective approach to clinical research-experienced at National and global level……………….

O autorze

Dr. Basavarajaiah D. M. working as an Associate Professor and Head, Department of Statistics and Computer Science, Karnataka Veterinary Animal and Fisheries Sciences University (B), Hebbal, Bangalore. He obtained Ph.D from National Institute of Epidemiology (NIE), ICMR, Chennai, (affiliated from University of Madras).His area of research heeds Statistical theory, Statistical modeling on high dimensional datasets of Agriculture, Medicine, Veterinary and animal Sciences. He penned seventy research articles and seven academic books published in national and reputed International publishers (Springer nature group). Serving as an editorial Board Member and Scientific Board advisor of various International indexed journals. Life Member of numerous academic organizations. Honoured several accolades for his academic and research Excellency “Chartered Scientist award stalwart by Science Council, United Kingdom in Collaboration with Royal Statistical Society. Best Reviewer award -2016‘TRANS STELLAR’ Journal Publications and Research Consultancy, TJPRC Ltd., (NAAS rated Journals), Fellow of Royal Statistical Society ,UK (London), Fellow of Mathematical Society ,UK (London), Bharathshikshratana and Indo-Dubai Achiever’s Pacific award honoured by Global Society of health and educational growth new Delhi, Best reviewer-2015, Best Scientific Board advisor - 2016 and Best editorial and researcher award bestowed by International academy of Engineering Science and technology, USA. He delegate power as an active member of Board of Studies and Academic Council of various Universities.

Professsor Narasimha Murthy is a well-known academician and researcher, Former Scientist ‘G’ (Director Grade cadre), National Institute of Epidemiology of ICMR, Chennai. Now, National Level Monitor, National Health Mission, MOH&FW, Government of India. He obtained PhD from International Institute for Population Science (IIPS), affiliated to Bombay University (1985). His areas of research are mainly Mathematical Statistics, Operational research, Clinical research, Public health, Demography and Vital Statistics, Mathematical modeling with respect to Medical Science and Public health. He penned more than 100 research articles published in reputed National and International Journals.  Serving as an editorial Board Member and Scientific Board advisor of various International indexed MCI and UGC recognized journals. Life Member of various academic organizations and professional societies. He honoured several accolades for his academic and research Excellency viz Prof. R. N. Srivastava gold medal award, ‘Bharat Jyothi Award’, ‘Best Citizens of India award etc. He serves as a member of Board of Studies of various National Universities (University of Madras, Acharya Nagarjuna University &University of Kerala) and also a visiting emeritus Professor of Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, North Carolina University USA, etc. Reviewer of National and International Journals.