Grant Number:	5R01CA018332-24 Interpret this number
Primary Investigator:	De Mets, David
Organization:	University Of Wisconsin Madison
Project Title:	Statistical Problems in Cancer Research
Fiscal Year:	1998

DESCRIPTION: Therapeutic and prevention clinical trials in cancer and other major diseases with mortality or irreversible morbidity are typically monitored to detect early evidence of benefit or harm for ethical and scientific reasons. However, repeated interim analyses using conventional statistical methods will increase the likelihood of false positive claims of treatment effect. In 1983, Lan and DeMets (Biometrika) extended earlier work of Pocock (1977), O'Brien and Fleming (1979) and others by proposing a flexible group sequential plan using an alpha spending function. In the previous proposal, we extended the application of the alpha spending function to repeated measure designs using linear mixed effects regression models and ordinal regression moods. Trials early may exaggerate treatment benefits or harm even though the hypothesis of no effect has been rejected. In this proposal, we further evaluate the degree of bias in the estimate of treatment effect and propose correction estimators for the linear mixed effects model and the proportional hazards model in survival. However, use of such models in either a sequential or non-sequential setting require that certain model assumptions be met, such as linearity or proportional hazards. We also propose developing sequential versions existing goodness of fit tests for these models such that inadequacy of the models can be identified early in the interim monitoring. Both the bias correction estimates and the sequential goodness of fit tests will be evaluated for common spending functions, various patterns of interim analyses, size of trials and robustness to model assumptions.




Increasing The Sample Size When The Unblinded Interim Result Is Promising
Authors: Chen Y.H. , DeMets D.L. , Lan K.K. .
Source: Statistics In Medicine, 2004-04-15 00:00:00.0; 23(7), p. 1023-38.
PMID: 15057876
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Surrogate End Points In Clinical Trials: Are We Being Misled?
Authors: Fleming T.R. , DeMets D.L. .
Source: Annals Of Internal Medicine, 1996-10-01 00:00:00.0; 125(7), p. 605-13.
PMID: 8815760
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Self-modelling With Random Shift And Scale Parameters And A Free-knot Spline Shape Function
Authors: Lindstrom M.J. .
Source: Statistics In Medicine, 1995-09-30 00:00:00.0; 14(18), p. 2009-21.
PMID: 8677401
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Group Sequential Comparison Of Changes: Ad-hoc Versus More Exact Method
Authors: Lee J.W. , DeMets D.L. .
Source: Biometrics, 1995 Mar; 51(1), p. 21-30.
PMID: 7766776
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Global Comparison Of Radiation And Chemotherapy Dose-response Curves With A Test For Interaction
Authors: Lindstrom M.J. , Kunugi K.A. , Kinsella T.J. .
Source: Radiation Research, 1993 Aug; 135(2), p. 269-77.
PMID: 7690150
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Sample Size Determination For Group Sequential Clinical Trials With Immediate Response
Authors: Kim K. , Demets D.L. .
Source: Statistics In Medicine, 1992 Jul; 11(10), p. 1391-9.
PMID: 1518999
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Analysis Of Longitudinal Data With Unmeasured Confounders
Authors: Palta M. , Yao T.J. .
Source: Biometrics, 1991 Dec; 47(4), p. 1355-69.
PMID: 1786323
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Nonlinear Mixed Effects Models For Repeated Measures Data
Authors: Lindstrom M.L. , Bates D.M. .
Source: Biometrics, 1990 Sep; 46(3), p. 673-87.
PMID: 2242409
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Group Sequential Procedures: Calendar Versus Information Time
Authors: Demets D.L. .
Source: Statistics In Medicine, 1989 Oct; 8(10), p. 1191-8.
PMID: 2814068
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Changing Frequency Of Interim Analysis In Sequential Monitoring
Authors: Lan K.K. , DeMets D.L. .
Source: Biometrics, 1989 Sep; 45(3), p. 1017-20.
PMID: 2790114
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Design And Analysis Of Phase I Clinical Trials
Authors: Storer B.E. .
Source: Biometrics, 1989 Sep; 45(3), p. 925-37.
PMID: 2790129
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Confidence Intervals Following Group Sequential Tests In Clinical Trials
Authors: Kim K. , DeMets D.L. .
Source: Biometrics, 1987 Dec; 43(4), p. 857-64.
PMID: 3427170
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Practical Aspects In Data Monitoring: A Brief Review
Authors: Demets D.L. .
Source: Statistics In Medicine, 1987 Oct-Nov; 6(7), p. 753-60.
PMID: 3321314
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Some Considerations In The Analysis Of Rates Of Change In Longitudinal Studies
Authors: Palta M. , Cook T. .
Source: Statistics In Medicine, 1987 Jul-Aug; 6(5), p. 599-611.
PMID: 3659670
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Methods For Combining Randomized Clinical Trials: Strengths And Limitations
Authors: Demets D.L. .
Source: Statistics In Medicine, 1987 Apr-May; 6(3), p. 341-50.
PMID: 3616287
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Use Of Logrank Tests And Group Sequential Methods At Fixed Calendar Times
Authors: DeMets D.L. , Gail M.H. .
Source: Biometrics, 1985 Dec; 41(4), p. 1039-44.
PMID: 4096915
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Investigating Maximum Power Losses In Survival Studies With Nonstratified Randomization
Authors: Palta M. .
Source: Biometrics, 1985 Jun; 41(2), p. 497-504.
PMID: 4027324
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A Biological Marker Model For Predicting Disease Transitions
Authors: Klein J.P. , Klotz J.H. , Grever M.R. .
Source: Biometrics, 1984 Dec; 40(4), p. 927-36.
PMID: 6598390
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