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(1890в1962) 17в18 Fisherвs exact test 184 improving 191 Fisherвs hypothesis testing 49 fixed combination therapy 463 fixed-effectrandom-effect models, multicentre trials 224в5 flexible designs controversies, sequential trials 310в13 Food and Drugs Administration see FDA (Food and Drugs Administration) footpoint 353 free combination therapy (or drug) 318, 463 frequentist statistics 464 basic principles 47в8 and hypothesis testing 48 null hypothesis 48 subgroup issues 138 versus Bayesian statistics 5, 18, 21, 51 futility 464 stopping for 300 12в13 160в1 Page 493 ппппGalton, Francis Cialis viagra online 16в17 general and generalized linear models 343в4 genetics 434в7 alleles 434 autosomal dominant inheritance Cialis viagra online 435 autosomal recessive inheritance (ARI) 435 cialis viagra online phenotype 436 gene-based therapy, economic case hierarchical generalized approach (HGLM) (Lee and Nelder) 291 Hill equation 342 historical controls 465 Holmвs procedure 153 448в50 gene-by-treatment interaction genetic variability genome 434 genotype 434 genotypic score genotyping patients 428 HardyвWeinberg (H-W) equilibrium 436в7, 445 heterozygous individuals 435 homozygous individuals 434 loci 434 penetrance 436 phenotype 434 phenotypic response whole-genome matching 441 see also pharmacogenetics (and pharmacogenomics) GENSTAT package 344 geometric distribution 392, 464 Glass effect size 259 GLIM programming language 343в4 global multivariate tests 153в4 global null hypotheses 158 global cialis viagra online tests 154 glossary 453в80 about intention to treat cialis viagra online missing data 165в7 causality issues 168в9 electronic monitoring 166 entry criteria 175 false inclusions 175в6 Gouldвs approach to compliance 169, 177 last observation carried forward (LOCF) analysis 170в1, 172 low-dose, slow-turnover chemical markers 166 missing at random 172в4 missing completely at random 171в2 missing not at random 174 models of missingness 170 gold-standard trials good clinical practice 464 group sequential methodtrials H-W (HardyвWeinberg) equilibrium 445 half-life (of elimination) 341, 464 HardyвWeinberg (H-W) cialis faz bem 445 harms 384, 464 hazard Cox regression hazard rate 388, 392в3, 465 proportional hazard model 388 heterozygous individuals 435 436в7, 436в7, 388 437в9 441в5 435в6 465 independence 465 independent events 44 individual null hypotheses 158 individual response measurement inference 51 design-based inference 40 inferential models 40 inferential statistics 422 and protocol 57 randomization-based 40 informed consent 71в2, 465 intention to cialis viagra online 239в40 Cialis viagra online 297в8, 464 homoscedasticity homozygous individuals 434 Hotellingвs T2 test 153 HPB (Health Protection Branch) 465 human genetic code see genetics hypothesis alternative hypothesis 454 see also null hypothesis hypothesis testtesting 465 in controlled clinical trials 48в9 and frequentist statistics 48 ICH (International Conference on Harmonisation) 3, 237, 465 imbalance with baselines 99в100 imputation, singlemultiple 174в5, 180в1 incidence of disease 387в8, 465 IND (Investigation New Drug) application 369в70 Index 489 116в19 Page 494 пппп490 Index intention to treat (Continued) multiple imputation 174в5 pattern-mixture models approach 169в70 and per-protocol analysis 177 post-baseline correction practical difficulties 176 rescue medication 177в8 Rubinвs reasons for missing treatments 169 selection models approach 169 tetrachoric correlation coefficient 173 theoretical justification 167в8 interactive effects 217, 220в1 treatment-by-centre interaction 227 International Conference on Harmonisation (ICH) 3, 237, 465 intersection null hypotheses 158 ab wieviel mg wirkt cialis probability 12 JeffreysвLindley paradox 206 joint probability 44, 164, 465 log scales 114 with scales of equivalence 245в6 log-transformation versus Fiellerвs theorem 368 logistic regression 143, 467 logit scaletransformation 114в16 Lordвs paradox 106в7 low-dose, slow-turnover chemical markers 166 KaplanвMeier estimator KaplanвMeier procedure Koseisho (Japan) 466 KullbackвLeibler (KL) approach label invariance, and two-sided tests 466 185, 270в1 257в8 laboratory data normal ranges cialis viagra online tables 385 tolerability data 385 384в5 385 laboratory shift tables 389в90 lack of compliance see intention to treat last observation carried forward (LOCF) analysis 170в1, Cialis viagra online Latin squares 274, 466 least-squares approach 265 life tables 387, 466 likelihood principle 466 manipulation of results and P-values 252, 254 publication bias 256в7 quality indices 265в6 random-effect variances result prediction 253в4 sequential 260в1 257 sequential trials 303 likelihood probabilities 45, 46, 466 Lindleyвs formulation 376в7 linear (dose-independent) drugs with sigma divided measures 129 two-trials rule 267 type A 251 type B 252 type C 252 weighting studies in fixed-effect 264 weighting used observed variances 264в5 see also pooling linear kinetics loading dose locus 467 log-AUCs 368в9 log-odds ratio 387, 467 466 340, 466 165в6, 168, 174 387, 465 466 367в8 340 cialis viagra online of results 257 MannвWhitneyвWilcoxon test MantelвHaenszel procedure 252 marginal probability 467 maximum likelihood 467 maximum tolerated dose maximum useful dose 318 mean 467 log-AUCs 368в9 mean square error measuring treatment effects 38в9 median 467 log-AUCs 368в9 medical statistics 19в20 meta-analysis 251в72 about meta-analysis 251в3 for analysing multicentre trials baseline risk 266, Cialis viagra online Bayesian 261в2 biasing cialis viagra online empirical weights and Cochrane collaboration (CC) concurrent control issues 266в7 definition 467в8 double-counting of trials 258 fixedrandom-effects 263 interpretation of effect sizes 258в60, Cialis viagra online 129, Cialis viagra online 317, 331, 467 139в40, 146в8, 467 262, 263в4 265 Page 495 ппппMHRA (Medicines and Healthcare products Index 491 multiple outcome requirements 208в9 multiple testing, dose-finding 322в4 Regulatory Agency) minimization 468 80 multiplication rule of probability 468 44, 455, Atkinsonвs proposals definition 468 efficiency 89в92 and treatment allocation multiplicity about multiplicity 149в50 Bayesian selection paradoxes Bayesian statistics issues 159 77в80 minimum effective dose 317, 331, 468 159в60 151в3, 162в3 missing data see intention to treat and Bonferroni corrections closed test procedure 158 and disjunctive power 152 and error rate control 155 false discovery rate (FDR) control 160в1 family-wise error rate (FWER) 149, 160в1 global multivariate tests 153в4 mixed model approaches modelsmodeling data generation cialis viagra online fixed-effectrandom-effect models general linear models 343 generalized linear models model-based inference 40 for multiplicity 154в5 nonlinear models 343в5 PD modelling 347в8 (PKPD) 337в58 population designs and models random effect models 320в2, 348в51 monitoring committeessponsor conflicts 306 monotonicity assumptions, dose-finding 332в3 mortality informationrates 387 standardized mortality ratio 388 multicentre trials about multicentre trials 213 Bayesian analogues 229в30 efficiency with unequal numbers estimator formulae 231в2 exploitation of centre to centre effects 228в9 fixed-effectrandom-effect models 224в5 fixedrandom-effect estimators 222в4 individual centre studies.

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