Type I Error Considerations in Master Protocols With Common Control in Oncology Trials: Report of an American Statistical Association Biopharmaceutical Section Open Forum Discussion

Author(s):  
Rajeshwari Sridhara ◽  
Olga Marchenko ◽  
Qi Jiang ◽  
Richard Pazdur ◽  
Martin Posch ◽  
...  
Biostatistics ◽  
2019 ◽  
Author(s):  
Jon Arni Steingrimsson ◽  
Joshua Betz ◽  
Tianchen Qian ◽  
Michael Rosenblum

Summary We consider the problem of designing a confirmatory randomized trial for comparing two treatments versus a common control in two disjoint subpopulations. The subpopulations could be defined in terms of a biomarker or disease severity measured at baseline. The goal is to determine which treatments benefit which subpopulations. We develop a new class of adaptive enrichment designs tailored to solving this problem. Adaptive enrichment designs involve a preplanned rule for modifying enrollment based on accruing data in an ongoing trial. At the interim analysis after each stage, for each subpopulation, the preplanned rule may decide to stop enrollment or to stop randomizing participants to one or more study arms. The motivation for this adaptive feature is that interim data may indicate that a subpopulation, such as those with lower disease severity at baseline, is unlikely to benefit from a particular treatment while uncertainty remains for the other treatment and/or subpopulation. We optimize these adaptive designs to have the minimum expected sample size under power and Type I error constraints. We compare the performance of the optimized adaptive design versus an optimized nonadaptive (single stage) design. Our approach is demonstrated in simulation studies that mimic features of a completed trial of a medical device for treating heart failure. The optimized adaptive design has $25\%$ smaller expected sample size compared to the optimized nonadaptive design; however, the cost is that the optimized adaptive design has $8\%$ greater maximum sample size. Open-source software that implements the trial design optimization is provided, allowing users to investigate the tradeoffs in using the proposed adaptive versus standard designs.


2000 ◽  
Vol 14 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Joni Kettunen ◽  
Niklas Ravaja ◽  
Liisa Keltikangas-Järvinen

Abstract We examined the use of smoothing to enhance the detection of response coupling from the activity of different response systems. Three different types of moving average smoothers were applied to both simulated interbeat interval (IBI) and electrodermal activity (EDA) time series and to empirical IBI, EDA, and facial electromyography time series. The results indicated that progressive smoothing increased the efficiency of the detection of response coupling but did not increase the probability of Type I error. The power of the smoothing methods depended on the response characteristics. The benefits and use of the smoothing methods to extract information from psychophysiological time series are discussed.


Methodology ◽  
2012 ◽  
Vol 8 (1) ◽  
pp. 23-38 ◽  
Author(s):  
Manuel C. Voelkle ◽  
Patrick E. McKnight

The use of latent curve models (LCMs) has increased almost exponentially during the last decade. Oftentimes, researchers regard LCM as a “new” method to analyze change with little attention paid to the fact that the technique was originally introduced as an “alternative to standard repeated measures ANOVA and first-order auto-regressive methods” (Meredith & Tisak, 1990, p. 107). In the first part of the paper, this close relationship is reviewed, and it is demonstrated how “traditional” methods, such as the repeated measures ANOVA, and MANOVA, can be formulated as LCMs. Given that latent curve modeling is essentially a large-sample technique, compared to “traditional” finite-sample approaches, the second part of the paper addresses the question to what degree the more flexible LCMs can actually replace some of the older tests by means of a Monte-Carlo simulation. In addition, a structural equation modeling alternative to Mauchly’s (1940) test of sphericity is explored. Although “traditional” methods may be expressed as special cases of more general LCMs, we found the equivalence holds only asymptotically. For practical purposes, however, no approach always outperformed the other alternatives in terms of power and type I error, so the best method to be used depends on the situation. We provide detailed recommendations of when to use which method.


Methodology ◽  
2015 ◽  
Vol 11 (1) ◽  
pp. 3-12 ◽  
Author(s):  
Jochen Ranger ◽  
Jörg-Tobias Kuhn

In this manuscript, a new approach to the analysis of person fit is presented that is based on the information matrix test of White (1982) . This test can be interpreted as a test of trait stability during the measurement situation. The test follows approximately a χ2-distribution. In small samples, the approximation can be improved by a higher-order expansion. The performance of the test is explored in a simulation study. This simulation study suggests that the test adheres to the nominal Type-I error rate well, although it tends to be conservative in very short scales. The power of the test is compared to the power of four alternative tests of person fit. This comparison corroborates that the power of the information matrix test is similar to the power of the alternative tests. Advantages and areas of application of the information matrix test are discussed.


2019 ◽  
Vol 227 (4) ◽  
pp. 261-279 ◽  
Author(s):  
Frank Renkewitz ◽  
Melanie Keiner

Abstract. Publication biases and questionable research practices are assumed to be two of the main causes of low replication rates. Both of these problems lead to severely inflated effect size estimates in meta-analyses. Methodologists have proposed a number of statistical tools to detect such bias in meta-analytic results. We present an evaluation of the performance of six of these tools. To assess the Type I error rate and the statistical power of these methods, we simulated a large variety of literatures that differed with regard to true effect size, heterogeneity, number of available primary studies, and sample sizes of these primary studies; furthermore, simulated studies were subjected to different degrees of publication bias. Our results show that across all simulated conditions, no method consistently outperformed the others. Additionally, all methods performed poorly when true effect sizes were heterogeneous or primary studies had a small chance of being published, irrespective of their results. This suggests that in many actual meta-analyses in psychology, bias will remain undiscovered no matter which detection method is used.


2014 ◽  
Vol 53 (05) ◽  
pp. 343-343

We have to report marginal changes in the empirical type I error rates for the cut-offs 2/3 and 4/7 of Table 4, Table 5 and Table 6 of the paper “Influence of Selection Bias on the Test Decision – A Simulation Study” by M. Tamm, E. Cramer, L. N. Kennes, N. Heussen (Methods Inf Med 2012; 51: 138 –143). In a small number of cases the kind of representation of numeric values in SAS has resulted in wrong categorization due to a numeric representation error of differences. We corrected the simulation by using the round function of SAS in the calculation process with the same seeds as before. For Table 4 the value for the cut-off 2/3 changes from 0.180323 to 0.153494. For Table 5 the value for the cut-off 4/7 changes from 0.144729 to 0.139626 and the value for the cut-off 2/3 changes from 0.114885 to 0.101773. For Table 6 the value for the cut-off 4/7 changes from 0.125528 to 0.122144 and the value for the cut-off 2/3 changes from 0.099488 to 0.090828. The sentence on p. 141 “E.g. for block size 4 and q = 2/3 the type I error rate is 18% (Table 4).” has to be replaced by “E.g. for block size 4 and q = 2/3 the type I error rate is 15.3% (Table 4).”. There were only minor changes smaller than 0.03. These changes do not affect the interpretation of the results or our recommendations.


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