Table Of ContentBIOPHARMACEUTICAL
SEQUENTIAL
STATISTICAL
APPLICATIONS
STATISTICS: Textbooks and Monographs
A Series Editedby
D. B. Owen, Coordinating Editor
Department ofStatistics
Southern Methodist University
Dallas, Texas
w.
R. G. Cornell, Associate Editor J. Kennedy, Associate Editor
for Biostatistics for Statistical Computing
University ofMichigan Iowa State University
A. M. Kshirsagar, Associate Editor E. G. Schilling, Associate Editor
for MultivariateAnalysis and for Statistical Quality Control
Experimental Design Rochester Institute ofTechnology
University ofMichigan
1. The Generalized Jackknife Statistic, H. L. GrayandW. R. Schucany
2. Multivariate Analysis, AnantM. Kshirsagar
3. Statistics and Society, Walter T. Federer
4. MultivariateAnalysis: A SelectedandAbstractedBibliography, 1967-1972,
Kocherlakota Subrahmaniam andKathleen Subrahmaniam
6. Design ofExperiments: A Realistic Approach, VirgilL.AndersonandRobert
A. McLean
6. Statistical and Mathematical Aspects of Pollution Problems, John W. Pratt
7. Introduction to Probability and Statistics (in two parts), Part I: Probability;
Part II: Statistics, Narayan C. Giri
8. Statistical Theory of the Analysis of Experimental Designs, J. Ogawa
9. Statistical Techniques in Simulation (in two parts), JackP. C. Kleijnen
10. Data Quality Control and Editing, Joseph I. Naus
11. Cost of Living Index Numbers: Practice, Precision, and Theory, Kali S.
Banerjee
12. Weighing Designs: For Chemistry, Medicine, Economics, Operations
Research, Statistics, Ka/iS. Banerjee
13. The Searchfor Oil: Some Statistical Methodsand Techniques, editedbyD.
B. Owen
14. Sample Size Choice: Chartsfor Experimentswith Linear Models, RobertE.
Odeh andMartin Fox
16. Statistical Methods for Engineers and Scientists, Robert M. Bethea, Ben-
jamin S. Duran, andThomas L. Boullion
16. Statistical Quality Control Methods, Irving W. Burr
17. On the History of Statistics and Probability, editedbyD. B. Owen
18. Econometrics, PeterSchmidt
19. Sufficient Statistics: Selected Contributions, Vasant S. Huzurbazar (edited
byAnantM. Kshirsagar)
20. Handbook of Statistical Distributions, Jagdish K. Patel, C. H. Kapadia, and
D. B. Owen
21. Case Studies in Sample Design, A. C. Rosander
22. Pocket Book of Statistical Tables, compiledbyR. E. Odeh, D. B. Owen, Z.
W. Birnbaum, andL. Fisher
23. TheInformation inContingencyTables,D. V. GokhaleandSolomonKullback
24. Statistical Analysis of Reliability and Life-Testing Models: Theory and
Methods, LeeJ. Bain
26. Elementary Statistical Quality Control, Irving W. Burr
26. An Introduction to Probability and Statistics Using BASIC, Richard A.
Groeneveld
27. Basic Applied Statistics, B. L. Raktoe andJ. J. Hubert
28. A Primer in Probability, Kathleen Subrahmaniam
29. Random Processes: A First Look, R. Syski
30. Regression Methods: A Tool for DataAnalysis, RudolfJ. FreundandPaulD.
Minton
31. Randomization Tests, Eugene S. Edgington
32. Tablesfor NormalTolerance Limits, SamplingPlansandScreening,RobertE.
Odeh andD. B. Owen
33. Statistical Computing, William J. Kennedy, Jr., andJamesE. Gentle
34. RegressionAnalysisandItsApplication: A Data-OrientedApproach, Richard
F. GunstandRobertL. Mason
36. Scientific Strategies to Save Your Life, I. D. J. Bross
36. StatisticsinthePharmaceuticalIndustry,editedbyC. RalphBuncherandJia-
Yeong Tsay
37. Sampling from a Finite Population, J. Hajek
38. Statistical Modeling Techniques, S. S. Shapiro
39. Statistical Theory and Inference in Research, T. A. BancroftandC.-P. Han
40. HandbookoftheNormalDistribution, JagdishK. PatelandCampbellB. Read
41. Recent Advances in Regression Methods, Hrishikesh D. Vinod andAman
Ullah
42. Acceptance Sampling in Quality Control, Edward G. Schilling
43. The Randomized Clinical Trial and Therapeutic Decisions, edited by Niels
Tygstrup, John M Lachin, andErik Juhl
44. Regression Analysis of Survival Data in Cancer Chemotherapy, Walter H.
Carter, Jr., Galen L. Wampler, andDonaldM. Stablein
46. A Course in Linear Models,AnantM. Kshirsagar
46. Clinical Trials: Issues and Approaches, edited by Stanley H. Shapiro and
Thomas H. Louis
47. Statistical Analysis of DNA Sequence Data, editedbyB. S. Weir
48. Nonlinear Regression Modeling: A Unified Practical Approach, David A.
Ratkowsky
49. Attribute Sampling Plans, Tables of Tests and Confidence Limits for
Proportions, RobertE. Odeh andD. B. Owen
60. Experimental Design, Statistical Models, and Genetic Statistics, edited by
Klaus Hinkelmann
61. Statistical Methods for Cancer Studies, editedbyRichard G. Cornell
62. Practical Statistical Sampling for Auditors, ArthurJ. Wilburn
63. Statistical Methods for Cancer Studies, editedby EdwardJ. Wegman and
James G. Smith
64. Self-Organizing Methods in Modeling: GMDH Type Algorithms, editedby
StanleyJ. Farlow
66. Applied Factorial and Fractional Designs, Robert A. McLean and Virgil L.
Anderson
66. DesignofExperiments: RankingandSelection, editedbyThomasJ. Santner
andAjitC. Tamhane
67. Statistical Methods for Engineers and Scientists: Second Edition, Revised
and Expanded, Robert M. Bethea, Benjamin S. Duran, and Thomas L.
Boullion
68. Ensemble Modeling: Inference from Small-Scale Properties to Large-Scale
Systems,Alan E. GelfandandCrayton C. Walker
69. Computer Modeling for Business and Industry, Bruce L. Bowerman and
Richard T. O'Connell
60. Bayesian Analysis of Linear Models, Lyle D. Broemeling
61. Methodological Issues for Health Care Surveys, Brenda Cox and Steven
Cohen
62. Applied Regression Analysis and Experimental Design, RichardJ. Brook and
Gregory C. Arnold
63. Statpal: A Statistical Packagefor Microcomputers-PC-DOSVersionforthe
IBM PC and Compatibles, Bruce J. ChalmerandDavid G. Whitmore
64. Statpal: A StatisticalPackageforMicrocomputers-Apple VersionfortheII,
II+, and lie, David G. Whitmore andBruce J. Chalmer
66. Nonparametric Statistical Inference: Second Edition, Revised and Ex
panded, Jean Dickinson Gibbons
66. Design and Analysis of Experiments, Roger G. Petersen
67. StatisticalMethodsforPharmaceuticalResearchPlanning, Sten W. Bergman
andJohn C. Gittins
68. Goodness-of-Fit Techniques, editedbyRalph B. D'Agostino andMichaelA.
Stephens
69. Statistical Methods in Discrimination Litigation, editedby D. H. Kaye and
MikelAickin
70. Truncated and Censored Samples from Normal Populations, Helmut
Schneider
71. Robust Inference, M. L. Tiku, W. Y. Tan, andN. Balakrishnan
72. StatisticalImageProcessingandGraphics, editedbyEdwardJ. Wegmanand
Douglas J. DePriest
73. Assignment Methods in Combinatorial Data Analysis, LawrenceJ. Hubert
74. Econometrics and Structural Change, LyleD. Broemeling andHirokiTsurumi
76. Multivariate Interpretation of Clinical Laboratory Data, Adelin Albert and
Eugene K. Harris
76. Statistical Tools for Simulation Practitioners, JackP. C. Kleijnen
77. Randomization Tests: Second Edition, Eugene S. Edgington
78. A Folio of Distributions: A Collection ofTheoretical Quantile-Quantile Plots,
EdwardB. Fowlkes
79. Applied Categorical Data Analysis, DanielH. Freeman, Jr.
80. SeeminglyUnrelatedRegressionEquationsModels: EstimationandInference,
Virendra K. SrivastavaandDavidE. A. Giles
81. Response Surfaces: Designs and Analyses, Andre /. Khuri and John A.
Cornell
82. Nonlinear Parameter Estimation: An Integrated System in BASIC, John C.
Nash andMary Walker-Smith
83. Cancer Modeling, editedbyJamesR. Thompson andBarry W. Brown
84. Mixture Models: Inference and Applications to Clustering, Geoffrey J.
McLachlan andKayeE. Basford
86. Randomized Response: Theory and Techniques,Arijit ChaudhuriandRahul
Mukerjee
86. Biopharmaceutical Statisticsfor Drug Development, editedbyKarlE. Peace
87. PartsperMillion Valuesfor Estimating Quality Levels,RobertE. OdehandD.
B. Owen
88. Lognormal Distributions: Theory andApplications, editedbyEdwin L. Crow
andKunio Shimizu
89. Properties of Estimators for the Gamma Distribution, K. O. Bowman andL.
R. Shenton
90. Spline Smoothing and Nonparametric Regression, RandallL. Eubank
91. Linear Least Squares Computations, R. W. Farebrother
92. Exploring Statistics, DamarajuRaghavarao
93. AppliedTimeSeriesAnalysisforBusinessandEconomicForecasting,SufiM.
Nazem
94. BayesianAnalysis ofTime SeriesandDynamic Models,editedby JamesC.
Spall
96. The Inverse Gaussian Distribution: Theory, Methodology, andApplications,
RajS. Chhikara andJ. LeroyFolks
96. Parameter Estimation in Reliability and Life Span Models,A. Clifford Cohen
andBettyJones Whitten
97. Pooled Cross-Sectional and Time Series Data Analysis, Terry E. Dielman
98. Random Processes: A FirstLook, SecondEdition, RevisedandExpanded, R.
Syski
99. Generalized Poisson Distributions: Properties andApplications, P. C. Consul
100. Nonlinear l,,-Norm Estimation, Rene Gonin andArthurH. Money
101. Model Discrimination for Nonlinear Regression Models, Dale S. Borowiak
102. Applied Regression Analysis in Econometrics, HowardE. Doran
103. Continued Fractions in Statistical Applications, K. O. Bowman and L. R.
Shenton
104. Statistical Methodology in the Pharmaceutical Sciences, DonaldA. Berry
106. Experimental Design in Biotechnology, PerryD. Haaland
106. StatisticalIssuesinDrugResearchandDevelopment, editedbyKarlE. Peace
107. Handbook of Nonlinear Regression Models, DavidA. Ratkowsky
108. Robust Regression: Analysis and Applications, edited by Kenneth D.
LawrenceandJeffreyL. Arthur
109. Statistical Design and Analysis of Industrial Experiments, edited by Subir
Ghosh
112. DataQualityControl: TheoryandPragmatics,editedbyGunarE. Liepinsand
V. R. R. Uppuluri
113. Engineering Qualityby Desig~: Interpreting the Taguchi Approach, Thomas
B. Barker
114. SurvivorshipAnalysisforClinical Studies,EugeneK. HarrisandAdelinAlbert
116. StatisticalAnalysisofReliabilityandLife-TestingModels:SecondEdition,Lee
J. Bain andMax Engelhardt
116. Stochastic Models of Carcinogenesis, Wai-Yuan Tan
117. Statistics and Society: Data Collection and Interpretation: Second Edition,
Revised and Expanded, Walter T. Federer
118. Handbook of Sequential Analysis, B. K. Ghosh andP. K. Sen
119. Truncated and Censored Samples: Theory and Applications, A. Clifford
Cohen
120. Survey Sampling Principles, E. K. Foreman
121. Applied Engineering Statistics, RobertM. BetheaandR. RussellRhinehart
122. Sample Size Choice: Charts for Experiments with Linear Models: Second
Edition, RobertE. Odeh andMartin Fox
123. Handbook of the Logistic Distribution, editedbyN. Balakrishnan
124. Fundamentals of Biostatistical Inference, Chap T. Le
126. Correspondence Analysis Handbook, J.-P. Benzecri
126. QuadraticFormsinRandomVariables:TheoryandApplications,A.M. Mathai
andSerge B. Provost
127. Confidence Intervals on Variance Components, by Richard K. Burdick and
FrankA. Graybill
128. BiopharmaceuticalSequentialStatisticalApplications, editedbyKarlE.Peace
129. Item Response Theory: ParameterEstimation Techniques, byFrankB. Baker
Additional Volumes in Preparation
Nonparametric StatisticalInference:ThirdEdition, RevisedandExpanded,by
Jean Dickinson Gibbons andSubhabrata Chakraborti
Design and Analysis of Bioavailability andBioequivalence Studies,byShein
Chung ChowandJen-PeiLiu
SurveySampling:TheoryandMethods,byArijitChaudhuriandHorstStenger
BivariateDiscreteDistribution, bySubrahmaniamKocherlakotaandKathleen
Kocherlakota
BIOPHARMACEUTICAL
SEQUENTIAL
STATISTICAL
APPLICATIONS
edited by
E.
KARL PEACE
BiopharmaceuticalResearchConsultants,Inc.
AnnArbor, Michigan
Marcel Dekker, Inc. New York • Basel • Hong Kong
LibraryofCongressCataloging-in-PublicationData
Biopharmaceutical sequential statistical applications/edited byKarl
E. Peace.
p. cm.- (Statistics, textbooksandmonographs; v. 128)
Includesbibliographical referencesand index.
ISBN0-8247-8628-9
1. Drugs--Testing--Statisticalmethods. 2. Sequential analysis.
I. Peace,Karl E. II. ~ries.
[DNLM: 1. Biophannaceutics. 2. Clinical Trials. 3. Drug
Evaluation. 4. Statistics. QV 771 B6153]
RM307.27.B55 1992
615'.1901'072--dc20
DNLM/DLC 92-4530
eIP
This bookis printed on acid-free paper.
Copyright ©1992 byMarcel Dekker, Inc. All rights reserved.
Neither this book nor any part may be reproduced or transmitted in any form
or by any means, electronic or mechanical, including photocopying, micro
filming, and recording, or by any information storage and retrieval system,
withoutpermission in writing from the publisher.
Marcel Dekker, Inc.
270Madison Avenue, New York, New York 10016
Currentprinting (lastdigit)
109 87 6 54 32 1
Printed in the United StatesofAmerica
Preface
Successful drug, biological, and medical device development for human use
requires aggressive, highly dedicated, competent, and diversified discovery,
basic research program teams, clinical development teams, and associated
research programs and clinical development plans. These programs and plans
must reflect good science and adequately address requirements of regulatory
agencies for approval to market.
The pharmaceutical industry is highly competitive. There are enormous
pressures and incentives to make the regulatory dossier available for registra
tional filing as early as possible. Although speed is of the essence, speed in
the absence of quality is likely to require a longer development time. Many
have heard the saying "Never enough time to do it right, always enough time
to do it over." Sequential statistical procedures, when incorporated into quality
research anddevelopmentprograms, representone way ofpossibly making the
regulatory dossier available more rapidly.
Incorporating sequential procedures into pharmaceutical research and
development programs is not to be taken lightly, nor is it without risks. Good
planning, execution, monitoring, data collection and management, statistical
analysis, communication and report writing skills, and resources are required.
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