• Communications for Statistical Applications and Methods
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• v.28 no.5
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• pp.411-424
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• 2021

Inference following two-stage adaptive designs (also known as two-stage randomization designs) with survival endpoints usually focuses on estimating and comparing survival distributions for the different treatment strategies. The aim is to identify the treatment strategy(ies) that leads to better survival of the patients. The objectives of this study were to assess the performance three commonly cited methods for estimating survival distributions in two-stage randomization designs. We review three non-parametric methods for estimating survival distributions in two-stage adaptive designs and compare their performance using simulation studies. The simulation studies show that the method based on the marginal mean model is badly affected by high censoring rates and response rate. The other two methods which are natural extensions of the Nelson-Aalen estimator and the Kaplan-Meier estimator have similar performance. These two methods yield survival estimates which have less bias and more precise than the marginal mean model even in cases of small sample sizes. The weighted versions of the Nelson-Aalen and the Kaplan-Meier estimators are less affected by high censoring rates and low response rates. The bias of the method based on the marginal mean model increases rapidly with increase in censoring rate compared to the other two methods. We apply the three methods to a leukemia clinical trial dataset and also compare the results.

• Communications for Statistical Applications and Methods
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• v.24 no.6
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• pp.561-581
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• 2017

Bayesian statistics can play a key role in the design and analysis of clinical trials and this has been demonstrated for medical device trials. By 1995 Bayesian statistics had been well developed and the revolution in computing powers and Markov chain Monte Carlo development made calculation of posterior distributions within computational reach. The Food and Drug Administration (FDA) initiative of Bayesian statistics in medical device clinical trials, which began almost 20 years ago, is reviewed in detail along with some of the key decisions that were made along the way. Both Bayesian hierarchical modeling using data from previous studies and Bayesian adaptive designs, usually with a non-informative prior, are discussed. The leveraging of prior study data has been accomplished through Bayesian hierarchical modeling. An enormous advantage of Bayesian adaptive designs is achieved when it is accompanied by modeling of the primary endpoint to produce the predictive posterior distribution. Simulations are crucial to providing the operating characteristics of the Bayesian design, especially for a complex adaptive design. The 2010 FDA Bayesian guidance for medical device trials addressed both approaches as well as exchangeability, Type I error, and sample size. Treatment response adaptive randomization using the famous extracorporeal membrane oxygenation example is discussed. An interesting real example of a Bayesian analysis using a failed trial with an interesting subgroup as prior information is presented. The implications of the likelihood principle are considered. A recent exciting area using Bayesian hierarchical modeling has been the pediatric extrapolation using adult data in clinical trials. Historical control information from previous trials is an underused area that lends itself easily to Bayesian methods. The future including recent trends, decision theoretic trials, Bayesian benefit-risk, virtual patients, and the appalling lack of penetration of Bayesian clinical trials in the medical literature are discussed.