New directions in adaptive designs

In any sequential medical experiment on a cohort of human beings, there is an ethical imperative to provide the best possible medical care for the individual patient. This ethical imperative may be compromised if a randomization scheme involving 50-50 allocation is used as accruing evidence begins to favor (albeit not yet conclusively) one experimental therapy over another. Adaptive designs have long been proposed to remedy this situation. An adaptive design seeks to skew assignment probabilities to favor the treatment performing best thus far in the study, proportionately to the magnitude of the treatment effect. Current researchers in adaptive designs are attempting to provide physicians with a wide choice of design options, and to address practical and ethical concerns within a rigorous mathematical framework. This paper focuses on several broad families of designs, including urn models, random walk rules and other rules. Numerous examples are given along with applications, dose-response studies, clinical trials for efficacy and combined toxicity-efficacy studies.

[1]  Alexander M. Mood,et al.  A Method for Obtaining and Analyzing Sensitivity Data , 1948 .

[2]  J. Doob.  Stochastic processes , 1953 .

[3]  A. Dvoretzky.  On Stochastic Approximation , 1956 .

[4]  F. J. Anscombe.  Sequential Medical Trials , 1963 .

[5]  T. Colton.  A Model for Selecting One of Two Medical Treatments , 1963 .

[6]  Samuel Karlin,et al.  A First Course on Stochastic Processes , 1968 .

[7]  N. Mantel.  Evaluation of survival data and two new rank order statistics arising in its consideration. , 1966, Cancer chemotherapy reports.

[8]  Samuel Karlin,et al.  Limit Theorems for the Split Times of Branching Processes , 1967 .

[9]  K. Athreya,et al.  Embedding of Urn Schemes into Continuous Time Markov Branching Processes and Related Limit Theorems , 1968 .

[10]  Max Halperin,et al.  An Adaptive Procedure for Sequential Clinical Trials , 1969 .

[11]  M. Zelen,et al.  Play the Winner Rule and the Controlled Clinical Trial , 1969 .

[12]  Thomas A. Louis,et al.  Sequential treatment allocation in clinical trials , 1971 .

[13]  J. Ware,et al.  Randomized clinical trials. Perspectives on some recent ideas. , 1976, The New England journal of medicine.

[14]  L. J. Wei,et al.  The Randomized Play-the-Winner Rule in Medical Trials , 1978 .

[15]  R. Tsutakawa.  Selection of Dose Levels for Estimating a Percentage Point of a Logistic Quantal Response Curve , 1980 .

[16]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data , 1980 .

[17]  R. Temple,et al.  Government Viewpoint of Clinical Trials , 1982 .

[18]  R. G. Cornell,et al.  Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study. , 1985, Pediatrics.

[19]  C. F. Wu,et al.  Efficient Sequential Designs with Binary Data , 1985 .

[20]  L. J. Wei,et al.  Exact two-sample permutation tests based on the randomized play-the-winner rule , 1988 .

[21]  Janis Hardwick,et al.  [Investigating Therapies of Potentially Great Benefit: ECMO]: Comment: Recent Progress in Clinical Trial Designs that Adapt for Ethical Purposes , 1989 .

[22]  B E Storer,et al.  Design and analysis of phase I clinical trials. , 1989, Biometrics.

[23]  Colin B. Begg,et al.  On inferences from Wei's biased coin design for clinical trials , 1990 .

[24]  L. J. Wei,et al.  Statistical Inference with Data-Dependent Treatment Allocation Rules , 1990 .

[25]  J O'Quigley,et al.  Continual reassessment method: a practical design for phase 1 clinical trials in cancer. , 1990, Biometrics.

[26]  S. Chevret,et al.  Methods for dose finding studies in cancer clinical trials: a review and results of a Monte Carlo study. , 1991, Statistics in medicine.

[27]  R. G. Cornell,et al.  Ethics and statistics in randomized clinical trials. , 1991, Statistical science : a review journal of the Institute of Mathematical Statistics.

[28]  D. Coad.  Sequential tests for an unstable response variable , 1991 .

[29]  J B Greenhouse,et al.  Bayesian methods for phase I clinical trials. , 1992, Statistics in medicine.

[30]  D. Coad,et al.  Data-dependent allocation rules a comparative study of some for bernoulli data , 1992 .

[31]  Roman Viveros,et al.  Statistical consequences of an adaptive treatment allocation in a clinical trial , 1993 .

[32]  S Chevret,et al.  The continual reassessment method in cancer phase I clinical trials: a simulation study. , 1993, Statistics in medicine.

[33]  William F. Rosenberger,et al.  Asymptotic Inference with Response-Adaptive Treatment Allocation Designs , 1993 .

[34]  J M Lachin,et al.  The use of response-adaptive designs in clinical trials. , 1993, Controlled clinical trials.

[35]  Nancy Flournoy,et al.  A Clinical Experiment in Bone Marrow Transplantation: Estimating a Percentage Point of a Quantal Response Curve , 1993 .

[36]  L V Rubinstein,et al.  A comparison of two phase I trial designs. , 1994, Statistics in medicine.

[37]  Douglas E. Faries,et al.  A Case Study of an Adaptive Clinical Trial in the Treatment of Out-Patients with Depressive Disorder , 1994 .

[38]  Nancy Flournoy,et al.  Random Walks for Quantile Estimation , 1994 .

[39]  T A Gooley,et al.  Simulation as a design tool for phase I/II clinical trials: an example from bone marrow transplantation. , 1994, Controlled clinical trials.

[40]  R. Gelber,et al.  Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. , 1994, The New England journal of medicine.

[41]  D. Faries,et al.  A randomized play-the-winner design for multi-arm clinical trials , 1994 .

[42]  E. Russek-Cohen,et al.  Selecting the best dose when a monotonic dose-response relation exists. , 1994, Statistics in medicine.

[43]  William F. Rosenberger,et al.  Toxicity in sequential dose-response experiments , 1995 .

[44]  Robert T. Smythe,et al.  Central limit theorems for urn models , 1996 .

[45]  Lee-Jen Wei,et al.  Play the winner for phase II/III clinical trials. , 1996, Statistics in medicine.

[46]  William F. Rosenberger,et al.  Estimation for an adaptive allocation design , 1997 .

[47]  S. Durham,et al.  A random walk rule for phase I clinical trials. , 1997, Biometrics.

[48]  William F. Rosenberger,et al.  Asymptotic normality of maximum likelihood estimators from multiparameter response-driven designs , 1997 .

[49]  H. Robbins.  Some aspects of the sequential design of experiments , 1952 .