A practical guide to Bayesian group sequential designs

Bayesian approaches to the monitoring of group sequential designs have two main advantages compared with classical group sequential designs: first, they facilitate implementation of interim success and futility criteria that are tailored to the subsequent decision making, and second, they allow inclusion of prior information on the treatment difference and on the control group. A general class of Bayesian group sequential designs is presented, where multiple criteria based on the posterior distribution can be defined to reflect clinically meaningful decision criteria on whether to stop or continue the trial at the interim analyses. To evaluate the frequentist operating characteristics of these designs, both simulation methods and numerical integration methods are proposed, as implemented in the corresponding R package gsbDesign. Normal approximations are used to allow fast calculation of these characteristics for various endpoints. The practical implementation of the approach is illustrated with several clinical trial examples from different phases of drug development, with various endpoints, and informative priors.

[1]  S J Pocock,et al.  The combination of randomized and historical controls in clinical trials. , 1976, Journal of chronic diseases.

[2]  Heinz Schmidli,et al.  The network meta-analytic-predictive approach to non-inferiority trials , 2013, Statistical methods in medical research.

[3]  Christy Chuang-Stein,et al.  The role of the minimum clinically important difference and its impact on designing a trial , 2011, Pharmaceutical statistics.

[4]  W. Alan Nicewander,et al.  A Consonance Criterion for Choosing Sample Size , 1997 .

[5]  Roger J Lewis,et al.  Bayesian decision-theoretic group sequential clinical trial design based on a quadratic loss function: a frequentist evaluation , 2007, Clinical trials.

[6]  Ludwig Kappos,et al.  Oral fingolimod (FTY720) for relapsing multiple sclerosis. , 2006, The New England journal of medicine.

[7]  D. Spiegelhalter,et al.  Summarizing historical information on controls in clinical trials , 2010, Clinical trials.

[8]  Anthony O'Hagan,et al.  The Rheumatoid Arthritis Drug Development Model: a case study in Bayesian clinical trial simulation , 2009, Pharmaceutical statistics.

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

[10]  M. A. Best.  Bayesian Approaches to Clinical Trials and Health‐Care Evaluation , 2005 .

[11]  O. Keene,et al.  Analysis of exacerbation rates in asthma and chronic obstructive pulmonary disease: example from the TRISTAN study , 2007, Pharmaceutical statistics.

[12]  F Barkhof,et al.  The distribution of new enhancing lesion counts in multiple sclerosis: further explorations , 2009, Multiple sclerosis.

[13]  Anthony O'Hagan,et al.  Assurance in clinical trial design , 2005 .

[14]  Florian Gerber,et al.  gsbDesign: An R Package for Evaluating the Operating Characteristics of a Group Sequential Bayesian Design , 2016 .

[15]  D. Gillen,et al.  Frequentist evaluation of group sequential clinical trial designs , 2007, Statistics in medicine.

[16]  J. Ibrahim,et al.  Power prior distributions for regression models , 2000 .

[17]  Vivian Gu,et al.  Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. , 2008, The New England journal of medicine.

[18]  Frank Bretz,et al.  Bayesian predictive power for interim adaptation in seamless phase II/III trials where the endpoint is survival up to some specified timepoint , 2007, Statistics in medicine.

[19]  Bradley P. Carlin,et al.  Bayesian Adaptive Methods for Clinical Trials , 2010 .

[20]  H Merabet,et al.  The design and analysis of sequential clinical trials , 2013 .

[21]  K. Carroll,et al.  Back to basics: explaining sample size in outcome trials, are statisticians doing a thorough job? , 2009, Pharmaceutical statistics.

[22]  Nigel Stallard,et al.  Decision‐making in a phase II clinical trial: a new approach combining Bayesian and frequentist concepts , 2005 .

[23]  Dana Quade,et al.  The Minimally Important Difference Significant Criterion for Sample Size , 1992 .

[24]  Dieter Houschke,et al.  The Impact of Incorporating Clinical Relevance on the Feasibility of Clinical Trials , 2008 .

[25]  A R Willan,et al.  Power function arguments in support of an alternative approach for analyzing management trials. , 1994, Controlled clinical trials.

[26]  T Friede,et al.  Blinded Sample Size Reestimation with Negative Binomial Counts in Superiority and Non-inferiority Trials , 2010, Methods of Information in Medicine.

[27]  Marc Vandemeulebroecke,et al.  Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial , 2012, Gut.

[28]  F. Barkhof,et al.  Modelling MRI enhancing lesion counts in multiple sclerosis using a negative binomial model: implications for clinical trials , 1999, Journal of the Neurological Sciences.

[29]  Bradley P Carlin,et al.  Hierarchical Commensurate and Power Prior Models for Adaptive Incorporation of Historical Information in Clinical Trials , 2011, Biometrics.

[30]  Gernot Wassmer,et al.  A Brief Review on Software Developments for Group Sequential and Adaptive Designs , 2006, Biometrical journal. Biometrische Zeitschrift.

[31]  Luca Roccatagliata,et al.  Magnetic resonance imaging as a potential surrogate for relapses in multiple sclerosis: A meta‐analytic approach , 2009, Annals of neurology.

[32]  Heinz Schmidli,et al.  Using historical control information for the design and analysis of clinical trials with overdispersed count data , 2013, Statistics in medicine.

[33]  P Armitage,et al.  Inference and decision in clinical trials. , 1989, Journal of clinical epidemiology.

[34]  B. Turnbull,et al.  Group Sequential Methods with Applications to Clinical Trials , 1999 .

[35]  Meinhard Kieser,et al.  Assessment of clinical relevance by considering point estimates and associated confidence intervals , 2005 .

[36]  Marc Vandemeulebroecke,et al.  Group Sequential and Adaptive Designs – A Review of Basic Concepts and Points of Discussion , 2008, Biometrical journal. Biometrische Zeitschrift.

[37]  R. Simon,et al.  Optimal two-stage designs for phase II clinical trials. , 1989, Controlled clinical trials.