A Position-Based Approach for Design and Analysis of Order-of-Addition Experiments

In many physical and computer experiments, the order in which the steps of a process are performed may have a substantial impact on the measured response. Often, the goal in these situations is to uncover the order that optimizes the response according to some metric. However, the brute force approach of performing all permutations quickly becomes impractical as the number of components in the process increases. Instead, we seek to develop order-of-addition experiments that choose an economically viable subset of permutations to test. The statistical literature on this topic is sparse, and many researchers rely on ad-hoc methods to study the effect of process order. In this work, we present a series of novel developments, including a modeling framework that exploits certain structures of the data, a method for constructing optimal designs under this proposed framework, and an evaluation of the performance and robustness of the constructed designs. We use data from a drug combination therapy problem to highlight the benefits of our approach.

[1]  Marte A. Ramírez-Ortegón,et al.  Circle detection using discrete differential evolution optimization , 2011, Pattern Analysis and Applications.

[2]  P. Sorger,et al.  Sequential Application of Anticancer Drugs Enhances Cell Death by Rewiring Apoptotic Signaling Networks , 2012, Cell.

[3]  Xianting Ding,et al.  Optimized combinations of bortezomib, camptothecin, and doxorubicin show increased efficacy and reduced toxicity in treating oral cancer , 2015, Anti-cancer drugs.

[4]  J. Voelkel,et al.  The design and analysis of order-of-addition experiments: An introduction and case study , 2019, Quality Engineering.

[5]  Lih-Yuan Deng,et al.  Minimum $G_2$-aberration for nonregular fractional factorial designs , 1999 .

[6]  Dennis K. J. Lin,et al.  Designs for order-of-addition experiments , 2020, Journal of applied statistics.

[7]  H. A. Barker Sum and product tables for Galois fields , 1986 .

[8]  R. Mukerjee,et al.  DESIGN EFFICIENCY UNDER MODEL UNCERTAINTY FOR NONREGULAR FRACTIONS OF GENERAL FACTORIALS , 2004 .

[9]  W. G. Hunter,et al.  Minimum Aberration 2 k–p Designs , 1980 .

[10]  Dennis K. J. Lin,et al.  Order-of-addition experiments: A review and some new thoughts , 2019, Quality Engineering.

[11]  Drew Seils,et al.  Optimal design , 2007 .

[12]  Uday K. Chakraborty,et al.  Advances in Differential Evolution , 2010 .

[13]  C. Radhakrishna Rao,et al.  Combinatorial arrangements analogous to orthogonal arrays , 1961 .

[14]  Jian Yang,et al.  Use of Fractional Factorial Designs in Antiviral Drug Studies , 2013, Qual. Reliab. Eng. Int..

[15]  Dennis K. J. Lin,et al.  Design of order-of-addition experiments , 2018, Biometrika.

[16]  Weng Kee Wong,et al.  Application of fractional factorial designs to study drug combinations , 2013, Statistics in medicine.

[17]  Wilfrido J. Paredes-García,et al.  Differential evolutionary algorithm in the construction process of optimal experimental designs , 2017, Commun. Stat. Simul. Comput..

[18]  Michael B. Miller Linear Regression Analysis , 2013 .

[19]  Rainer Storn,et al.  Differential Evolution – A Simple and Efficient Heuristic for global Optimization over Continuous Spaces , 1997, J. Glob. Optim..

[20]  Jennifer Werfel,et al.  Orthogonal Arrays Theory And Applications , 2016 .

[21]  Boxin Tang,et al.  GENERALIZED MINIMUM ABERRATION AND DESIGN EFFICIENCY FOR NONREGULAR FRACTIONAL FACTORIAL DESIGNS , 2002 .

[22]  Robert W. Mee Order-of-Addition Modeling , 2020 .

[23]  Hongquan Xu Minimum moment aberration for nonregular designs and supersaturated designs , 2001 .

[24]  Chih-Ming Ho,et al.  Output-driven feedback system control platform optimizes combinatorial therapy of tuberculosis using a macrophage cell culture model , 2016, Proceedings of the National Academy of Sciences.

[25]  Joseph G. Voelkel Discussion on “Order-of-Addition Experiments: A review and some new thoughts” , 2019 .

[26]  Hongquan Xu,et al.  A Component-Position Model, Analysis and Design for Order-of-Addition Experiments , 2020, Technometrics.

[27]  C. F. Jeff Wu,et al.  Experiments , 2021, Wiley Series in Probability and Statistics.

[28]  Changbao Wu,et al.  Fractional Factorial Designs , 2022 .

[29]  Weng Kee Wong,et al.  Recent developments in nonregular fractional factorial designs , 2008, 0812.3000.

[30]  Xianting Ding,et al.  Simultaneous Optimization of Drug Combination Dose‐Ratio Sequence with Innovative Design and Active Learning , 2020, Advanced Therapeutics.