Statistical Approaches to Interim Monitoring of Medical Trials: A Review and Commentary

Most medical trials are monitored for early evidence of treatment differences or harmful side effects. In this paper we review and critique various statistical approaches that have been proposed for the design and analysis of sequential experiments in medical applications. We discuss group sequential tests, stochastic curtailment, repeated confidence intervals, and Bayesian procedures. The role that a statistical stopping rule should play in the final analysis is examined.

[1]  J. Haybittle,et al.  Repeated assessment of results in clinical trials of cancer treatment. , 1971, The British journal of radiology.

[2]  John Bather.  Stoppping rules and ordered families of distributions , 1988 .

[3]  J. Lachin.  Sequential clinical trials for normal variates using interval composite hypotheses. , 1981, Biometrics.

[4]  K. K. Lan,et al.  Stochastically curtailed tests in long–term clinical trials , 1982 .

[5]  P. Armitage,et al.  Repeated Significance Tests on Accumulating Data When the Null Hypothesis is Not True , 1971 .

[6]  S J Pocock,et al.  Interim analyses for randomized clinical trials: the group sequential approach. , 1982, Biometrics.

[7]  Christopher Jennison,et al.  Efficient group sequential tests with unpredictable group sizes , 1987 .

[8]  S. Pocock,et al.  Clinical Trials: A Practical Approach , 1984 .

[9]  Eric V. Slud,et al.  Two-Sample Repeated Significance Tests Based on the Modified Wilcoxon Statistic , 1982 .

[10]  David L. DeMets,et al.  Asymmetric group sequential boundaries for monitoring clinical trials , 1982 .

[11]  M. Halperin,et al.  Stochastic curtailing for comparison of slopes in longitudinal studies. , 1987, Controlled clinical trials.

[12]  H. Robbins.  Statistical Methods Related to the Law of the Iterated Logarithm , 1970 .

[13]  J. Cornfield.  A BAYESIAN TEST OF SOME CLASSICAL HYPOTHESES- WITH APPLICATIONS TO SEQUENTIAL CLINICAL TRIALS , 1966 .

[14]  A. Lawrence Gould,et al.  Group sequential methods for clinical trials allowing early acceptance of Ho and incorporating costs , 1982 .

[15]  K K Lan,et al.  The B-value: a tool for monitoring data. , 1988, Biometrics.

[16]  D. Siegmund.  Sequential Analysis: Tests and Confidence Intervals , 1985 .

[17]  D M Barnes,et al.  Promising results halt trial of anti-AIDS drug. , 1986, Science.

[18]  Brown Bw,et al.  Confidence limits for probability of response in multistage phase II clinical trials. , 1985 .

[19]  Stephen L. George,et al.  Fundamentals of Clinical Trials. (2nd ed.). , 1987 .

[20]  B. Turnbull,et al.  Repeated confidence intervals for group sequential clinical trials. , 1984, Controlled clinical trials.

[21]  P K Andersen,et al.  Conditional power calculations as an aid in the decision whether to continue a clinical trial. , 1987, Controlled clinical trials.

[22]  E. Samuel-Cahn.  Comparisons of sequential two-sided tests for normal hypothesis , 1980 .

[23]  M A Fischl,et al.  The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. , 1987, The New England journal of medicine.

[24]  M. Stone,et al.  Marginalization Paradoxes in Bayesian and Structural Inference , 1973 .

[25]  S. Pocock.  Group sequential methods in the design and analysis of clinical trials , 1977 .

[26]  R. Madsen,et al.  P-Values for Multi-Stage and Sequential Tests. , 1981 .

[27]  Donald B. Rubin,et al.  Sensitivity of Bayes Inference with Data-Dependent Stopping Rules , 1984 .

[28]  A. Tsiatis,et al.  Approximately optimal one-parameter boundaries for group sequential trials. , 1987, Biometrics.

[29]  D J Spiegelhalter,et al.  Comparison of Bayesian with group sequential methods for monitoring clinical trials. , 1989, Controlled clinical trials.

[30]  K. K. Lan,et al.  Discrete sequential boundaries for clinical trials , 1983 .

[31]  Frederick Mosteller,et al.  Statistics and ethics in surgery and anesthesia. , 1977 .

[32]  Christopher Jennison,et al.  Confidence Intervals for a Binomial Parameter Following a Multistage Test With Application to MIL-STD 105D and Medical Trials , 1983 .

[33]  J. Whitehead,et al.  The analysis of sequential clinical trials , 1979 .

[34]  L. Walløe,et al.  Estimation of treatment difference following a sequential clinical trial , 1989 .

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

[36]  James O. Berger,et al.  Statistical Analysis and the Illusion of Objectivity , 1988 .

[37]  Choi Sc,et al.  Monitoring clinical trials based on predictive probability of significance. , 1989 .

[38]  J Whitehead,et al.  Group sequential clinical trials with triangular continuation regions. , 1983, Biometrics.

[39]  K McPherson,et al.  Statistics: the problem of examining accumulating data more than once. , 1974, The New England journal of medicine.

[40]  P. Armitage,et al.  Repeated Significance Tests on Accumulating Data , 1969 .

[41]  J Cornfield,et al.  The Bayesian outlook and its application. , 1969, Biometrics.

[42]  W. Dupont.  Sequential stopping rules and sequentially adjusted P values: does one require the other? , 1983, Controlled clinical trials.

[43]  P. Meier,et al.  Statistics and medical experimentation. , 1975, Biometrics.

[44]  F. Rockhold,et al.  Monitoring versus interim analysis of clinical trials: a perspective from the pharmaceutical industry. , 1989, Controlled clinical trials.

[45]  P. O'Brien,et al.  A multiple testing procedure for clinical trials. , 1979, Biometrics.

[46]  S G Hilsenbeck.  Early termination of a phase II clinical trial. , 1988, Controlled clinical trials.

[47]  W Koepcke,et al.  Analyses of group sequential clinical trials. , 1989, Controlled clinical trials.

[48]  K Kim,et al.  Confidence intervals following group sequential tests in clinical trials. , 1987, Biometrics.

[49]  P. Armitage,et al.  Sequential medical trials. 2nd edition. , 1975 .

[50]  J. Tukey.  Conclusions vs Decisions , 1960 .

[51]  Herman Chernoff,et al.  Sequential medical trials involving paired data , 1981 .

[52]  D L DeMets,et al.  An aid to data monitoring in long-term clinical trials. , 1982, Controlled clinical trials.

[53]  D. Duffy,et al.  Confidence Intervals for a Binomial Parameter Based on Multistage Tests , 1987 .

[54]  David L. DeMets,et al.  Group sequential methods for clinical trials with a one-sided hypothesis , 1980 .

[55]  J B Kadane,et al.  Progress toward a more ethical method for clinical trials. , 1986, The Journal of medicine and philosophy.

[56]  H. Wieand,et al.  The bias of the sample proportion following a group sequential phase II clinical trial. , 1989, Statistics in medicine.

[57]  S. Pocock,et al.  Stopping rules and estimation problems in clinical trials. , 1988, Statistics in medicine.

[58]  D L DeMets,et al.  Changing frequency of interim analysis in sequential monitoring. , 1989, Biometrics.

[59]  T R Fleming,et al.  Designs for group sequential tests. , 1984, Controlled clinical trials.

[60]  Sheldon M. Ross,et al.  Stochastic Processes , 2018, Gauge Integral Structures for Stochastic Calculus and Quantum Electrodynamics.

[61]  T. Lai.  Incorporating scientific, ethical and economic considerations into the design of clinical trials in the pharmaceutical industry: a sequential approach , 1984 .

[62]  David L. DeMets,et al.  Stopping guidelines vs stopping rules: a practitioner's point of view , 1984 .

[63]  Christopher Jennison,et al.  Interim analyses: the repeated confidence interval approach , 1989 .

[64]  P. Armitage,et al.  Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. , 1976, British Journal of Cancer.

[65]  P. O'Brien,et al.  Confidence intervals following group sequential tests. , 1986, Controlled clinical trials.

[66]  M. Pike,et al.  Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. , 1977, British Journal of Cancer.

[67]  D. Spiegelhalter,et al.  Monitoring clinical trials: conditional or predictive power? , 1986, Controlled clinical trials.

[68]  M. Chang,et al.  Confidence intervals for a normal mean following a group sequential test. , 1989, Biometrics.

[69]  J. Whitehead.  Supplementary analysis at the conclusion of a sequential clinical trial. , 1986, Biometrics.

[70]  R. Peto.  Discussion of 'On the Allocation of Treatments in Sequential Medical Trials' by J.A. Bather and 'The Search for Optimality in Clinical Trials' by P. Armitage , 1985 .

[71]  M. Halperin,et al.  Early Decision in a Censored Wilcoxon Two-Sample Test for Accumulating Survival Data , 1974 .

[72]  A. Petkau,et al.  Sequential testing of the equality of two survival distributions using the modified Savage statistic , 1978 .

[73]  William E. Strawderman,et al.  Complete Classes for Sequential Tests of Hypotheses , 1980 .

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

[75]  Pranab Kumar Sen,et al.  Nonparametric Testing Under Progressive Censoring* , 1973 .

[76]  David L. DeMets,et al.  Design and analysis of group sequential tests based on the type I error spending rate function , 1987 .

[77]  J. Berger.  Statistical Decision Theory and Bayesian Analysis , 1988 .

[78]  James O. Berger,et al.  STATISTICAL DECISION THEORY: FOUNDATIONS, CONCEPTS, AND METHODS , 1984 .

[79]  P. Armitage.  Sequential Medical Trials , 1961, Biomedicine / [publiee pour l'A.A.I.C.I.G.].

[80]  J. Whitehead,et al.  A FORTRAN program for the design and analysis of sequential clinical trials. , 1983, Computers and biomedical research, an international journal.

[81]  S. Rössner,et al.  Coronary Drug Project Research Group. , 1978, Atherosclerosis.

[82]  T R Fleming,et al.  Symmetric group sequential test designs. , 1989, Biometrics.

[83]  A A Tsiatis,et al.  Exact confidence intervals following a group sequential test. , 1984, Biometrics.

[84]  D. Siegmund.  Corrected diffusion approximations in certain random walk problems , 1979, Advances in Applied Probability.

[85]  D. Siegmund.  Estimation following sequential tests , 1978 .

[86]  P. Armitage,et al.  A family of closed sequential procedures , 1962 .

[87]  Anastasios A. Tsiatis,et al.  Exact confidence intervals following a group sequential trial: A comparison of methods , 1988 .

[88]  P. Armitage,et al.  NUMERICAL STUDIES IN THE SEQUENTIAL ESTIMATION OF A BINOMIAL PARAMETER , 1958 .

[89]  K K Lan,et al.  Monitoring boundaries for adverse effects in long-term clinical trials. , 1986, Controlled clinical trials.

[90]  Christopher Jennison,et al.  Repeated confidence intervals for the median survival time , 1985 .

[91]  C. Jennison,et al.  Group Sequential tests and Repeated Confidence Intervals , 1988 .

[92]  C. E. Davis,et al.  A two sample wilcoxon test for progressively censored data , 1978 .

[93]  D. Spiegelhalter,et al.  The Assessment of the Subjective Opinion and its Use in Relation to Stopping Rules for Clinical Trials , 1983 .

[94]  R. Madsen,et al.  P values for tests using a repeated significance test design , 1982 .

[95]  J. Cornfield.  Sequential Trials, Sequential Analysis and the Likelihood Principle , 1966 .

[96]  J. A. Bather,et al.  On the Allocation of Treatments in Sequential Medical Trials , 1985 .

[97]  M D Hughes,et al.  Practical problems in interim analyses, with particular regard to estimation. , 1989, Controlled clinical trials.

[98]  James M. Dickey,et al.  Scientific Reporting and Personal Probabilities: Student's Hypothesis , 1973 .

[99]  M. Evans,et al.  On principles and arguments to likelihood , 1986 .