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Design and Analysis of Vaccine Studies

:	M. Elizabeth Halloran, Ira M. Longini, Jr., Claudio J. Struchiner
:	Design and Analysis of Vaccine Studies
:	Springer-Verlag
:	9780387686363
:	1
:	CHF 189.40
:

:	Allgemeines
:	English

:	390
:	Wasserzeichen/DRM
:	PC/MAC/eReader/Tablet
:	PDF

As well as being a reference for the design, analysis, and interpretation of vaccine studies, the text covers all design and analysis stages, from vaccine development to post-licensure surveillance, presenting likelihood, frequentists, and Bayesian approaches.

	Preface	6
	Contents	9
	1 Introduction and Examples	17
	1.1 The Need of Vaccine Studies Framework	17
	1.2 Scope and Outline of the Book	23
	1.3 Concepts in Infectious Disease Research	26
	1.3.1 Transmission	26
	1.3.2 Time line of infection	27
	1.3.3 Basic reproductive number, R0 and generation interval, Tg	29
	1.4 Causal Inference and Vaccine Effects	31
	Problems	33
	2 Overview of Vaccine Effects and Study Designs	35
	2.1 Introduction	35
	2.2 Vaccine Effects of Interest	35
	2.3 Vaccine Efficacy for Susceptibility, VES (VESP)	37
	2.3.1 VES conditional on knowledge of exposure to infection	38
	2.3.2 VES not conditional on knowledge of exposure to infection	40
	2.4 Hierarchy of VES Measures	42
	2.5 Vaccine Efficacy for Infectiousness, VEI	43
	2.5.1 Estimating multiple levels of parameters	45
	2.6 Vaccine Efficacy for Progression or Pathogenesis, VEP	45
	2.7 Contact Rates and Exposure Efficacy	47
	2.8 Indirect, Total, and Overall Effectiveness	47
	2.8.1 Hypothetical example	49
	2.8.2 Influenza example	51
	2.9 Counting Process Models for Hierarchy of Parameters	51
	2.9.1 Contact, infection, susceptibility, and infectiousness processes	52
	2.9.1.1 Overview	52
	2.9.1.2 Notation and definitions	52
	2.9.1.3 Intensities for contact processes	53
	2.9.1.4 Intensities for infection processes	54
	2.9.2 Information levels and types of statistical analyses	54
	2.9.2.1 Level I	55
	2.9.2.2 Level II	56
	2.9.2.3 Level III	57
	2.9.2.4 Level IV	57
	2.9.3 Homogeneous mixing	59
	Problems	59
	3 Immunology and Early Phase Trials	62
	3.1 Immunology and Infection	63
	3.1.1 Innate and adaptive immune systems	63
	3.1.2 Immune response to infection	64
	3.1.3 Antibodies and epitopes	65
	3.2 Vaccines	66
	3.2.1 Smallpox	66
	3.2.2 Early development	67
	3.2.3 Recent developments and beyond	69
	3.2.4 Adjuvants	70
	3.3 Vaccine Safety	70
	3.4 Immune Assays	71
	3.4.1 Antibody assays	71
	3.4.2 T-cell assays	72
	3.5 Herd Immunity	73
	3.6 Early Phase Vaccine Studies	75
	3.7 Human Challenge Studies	76
	Problems	76
	4 Binomial and Stochastic Transmission Models	78
	4.1 Overview	78
	4.2 Contact Processes and Mixing Structures	79
	4.2.1 Random mixing	79
	4.2.2 Transmission units within populations	80
	4.2.3 Mutually exclusive subpopulations	81
	4.2.4 Population dynamics	82
	4.3 Probability of Discrete Infection Events	82
	4.3.1 Probability of infection in discrete time or contacts	82
	4.3.2 Other transmission models	84
	4.3.3 Probability of infection in continuous time	85
	4.3.4 Contacts with persons of unknown infection status	85
	4.4 Chain Binomial Models	86
	4.4.1 The Reed–Frost model	88
	4.4.1.1 History	90
	4.4.2 The Greenwood model	91
	4.4.3 Stochastic realizations of the Reed–Frost model	91
	4.5 Stochastic Simulation Models	93
	4.5.1 Endemic cholera and vaccination	94
	4.5.2 Use in study design	98
	Problems	98
	5 R0 and Deterministic Models	100
	5.1 Basic Reproductive Number	100
	5.1.1 R0 and public health	102
	5.2 Vaccination and R0	102
	5.2.1 The critical vaccination fraction and R0	103
	5.2.2 R with VES and VEI	105
	5.2.3 R0 and influenza vaccination	106
	5.3 Other Aspects of R0	109
	5.3.1 Evolution and R0	110
	5.3.2 Estimating R0 in real-time	111
	5.3.3 Caveats	111
	5.4 Deterministic Transmission Models	111
	5.4.1 Simple deterministic SIR model	112
	5.4.2 Dynamics of an epidemic	113
	5.4.3 Other simple models	114
	5.4.4 Within host dynamics	115
	5.5 Modeling Vaccination Programs	116
	Problems	117
	6 Evaluating Protective Effects of Vaccination	118
	6.1 Overview	118
	6.2 Estimating VES	119
	6.2.1 Absolute versus relative efficacy	120
	6.2.2 Types of studies	121
	6.2.2.1 Randomized versus observational cohort studies	122
	6.2.3 Estimation and inference	123
	6.3 Design Considerations	126
	6.3.1 Vaccines and vaccination schedule	126
	6.3.2 Study population	127
	6.3.2.1 Recruitment and vaccination	127
	6.3.3 Case definition	127
	6.3.4 Ascertainment of cases	127
	6.3.4.1 Safety and Immunogenicity	127
	6.3.5 Sample size calculations	128
	6.4 Examples of Randomized Trials	129
	6.4.1 Relative efficacy of pertussis vaccines in Senegal	129
	6.4.2 Absolute efficacy of pertussis vaccine in Sweden	131
	6.4.3 Absolute efficacy of live attenuated influenza vaccine in children	134
	6.4.4 Live attenuated influenza vaccine in adults without biological confirmation	135
	6.4.5 Relative efficacy of live and killed influenza vaccine in young children	137
	6.4.6 Oral cholera vaccines in Bangladesh	138
	6.4.7 Pneumococcal conjugate vaccine in California	140
	6.5 Report of a Study	141
	6.6 Reduction in Burden of Illness	142
	Problems	144
	7 Modes of Action and Time-Varying VES	145
	7.1 Mode of Action and Choice of Measures	145
	7.1.1 Leaky and all-or-none modes of action	146
	7.1.2 Implications for choice of efficacy measures	147
	7.1.3 Attack rates versus transmission probabilities	149
	7.1.3.1 Example	150
	7.2 Frailty Mixture Models for VES,	151
	7.2.1 Mixing models	151
	7.2.2 Frailty model	153
	7.2.2.1 Statistical inference	154
	7.2.3 Measles out