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1. Diagnostic Tools for Evaluating and Comparing Simulation-Optimization Algorithms

   https://doi.org/10.1287/ijoc.2022.1261  

   Eckman, David J.; Henderson, Shane G.; Shashaani, Sara (February 2023, INFORMS Journal on Computing)

   Simulation optimization involves optimizing some objective function that can only be estimated via stochastic simulation. Many important problems can be profitably viewed within this framework. Whereas many solvers—implementations of simulation-optimization algorithms—exist or are in development, comparisons among solvers are not standardized and are often limited in scope. Such comparisons help advance solver development, clarify the relative performance of solvers, and identify classes of problems that defy efficient solution, among many other uses. We develop performance measures and plots, and estimators thereof, to evaluate and compare solvers and diagnose their strengths and weaknesses on a testbed of simulation-optimization problems. We explain the need for two-level simulation in this context and provide supporting convergence theory. We also describe how to use bootstrapping to obtain error estimates for the estimators. History: Accepted by Bruno Tuffin, area editor for simulation. Funding: This work was supported by the National Science Foundation [Grants CMMI-2035086, CMMI-2206972, and TRIPODS+X DMS-1839346]. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplementary Information [ https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.1261 ] or is available from the IJOC GitHub software repository ( https://github.com/INFORMSJoC ) at [ http://dx.doi.org/10.5281/zenodo.7329235 ]. 

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2. RouteOpt: An Open-Source Modular Exact Solver for Vehicle Routing Problems

   https://doi.org/10.1287/ijoc.2025.1415  

   You, Zhengzhong; Yang, Yu (May 2026, INFORMS Journal on Computing)

   Despite significant advancements in exact methods for vehicle routing problems (VRPs) over the past three decades, there remains a lack of high-performing and accessible open-source solvers for researchers and practitioners. To bridge this gap, we introduce RouteOpt, the first open-source modular exact solver for VRPs, delivering state-of-the-art performance while maintaining a flexible and extensible structure. RouteOpt achieves the best performance reported in the literature on both the capacitated vehicle routing problem (CVRP) and the VRP with time windows. Crucially, its modular design allows users to develop and integrate customized branching, cutting-plane, and variable reduction modules to tackle a broad range of VRP variants. Furthermore, RouteOpt introduces a novel node restoration mechanism, enabling efficient parallel processing of a branch-and-bound tree. Leveraging this feature, we have for the first time proven the optimality of three open CVRP instances. By combining modularity, efficiency, and open accessibility, RouteOpt establishes itself as an invaluable platform for both academic research and real-world applications. The source code of RouteOpt and relevant data are publicly available in the RouteOpt repository. History: Accepted by Ted Ralphs, Area Editor for Software Tools. Funding: This work was supported by the Division of Civil, Mechanical and Manufacturing Innovation [Grant CMMI-2309667]. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2025.1415 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2025.1415 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ . 

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3. Efficient Nested Simulation Experiment Design via the Likelihood Ratio Method

   https://doi.org/10.1287/ijoc.2022.0392  

   Feng, Ben Mingbin; Song, Eunhye (June 2024, INFORMS Journal on Computing)

   In the nested simulation literature, a common assumption is that the experimenter can choose the number of outer scenarios to sample. This paper considers the case when the experimenter is given a fixed set of outer scenarios from an external entity. We propose a nested simulation experiment design that pools inner replications from one scenario to estimate another scenario’s conditional mean via the likelihood ratio method. Given the outer scenarios, we decide how many inner replications to run at each outer scenario as well as how to pool the inner replications by solving a bilevel optimization problem that minimizes the total simulation effort. We provide asymptotic analyses on the convergence rates of the performance measure estimators computed from the optimized experiment design. Under some assumptions, the optimized design achieves [Formula: see text] mean squared error of the estimators given simulation budget [Formula: see text]. Numerical experiments demonstrate that our design outperforms a state-of-the-art design that pools replications via regression. History: Accepted by Bruno Tuffin, Area Editor for Simulation. Funding: This work was supported by the National Science Foundation [Grant CMMI-2045400] and the Natural Sciences and Engineering Research Council of Canada [Grant RGPIN-2018-03755]. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.0392 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2022.0392 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ . 

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4. A Shrinkage Approach to Improve Direct Bootstrap Resampling Under Input Uncertainty

   https://doi.org/10.1287/ijoc.2022.0044  

   Song, Eunhye; Lam, Henry; Barton, Russell R (February 2024, INFORMS Journal on Computing)

   Discrete-event simulation models generate random variates from input distributions and compute outputs according to the simulation logic. The input distributions are typically fitted to finite real-world data and thus are subject to estimation errors that can propagate to the simulation outputs: an issue commonly known as input uncertainty (IU). This paper investigates quantifying IU using the output confidence intervals (CIs) computed from bootstrap quantile estimators. The standard direct bootstrap method has overcoverage due to convolution of the simulation error and IU; however, the brute-force way of washing away the former is computationally demanding. We present two new bootstrap methods to enhance direct resampling in both statistical and computational efficiencies using shrinkage strategies to down-scale the variabilities encapsulated in the CIs. Our asymptotic analysis shows how both approaches produce tight CIs accounting for IU under limited input data and simulation effort along with the simulation sample-size requirements relative to the input data size. We demonstrate performances of the shrinkage strategies with several numerical experiments and investigate the conditions under which each method performs well. We also show advantages of nonparametric approaches over parametric bootstrap when the distribution family is misspecified and over metamodel approaches when the dimension of the distribution parameters is high. History: Accepted by Bruno Tuffin, Area Editor for Simulation. Funding: This work was supported by the National Science Foundation [CAREER CMMI-1834710, CAREER CMMI-2045400, DMS-1854659, and IIS-1849280]. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.0044 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2022.0044 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ . 

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5. Combination Chemotherapy Optimization with Discrete Dosing

   https://doi.org/10.1287/ijoc.2022.0207  

   Ajayi, Temitayo; Hosseinian, Seyedmohammadhossein; Schaefer, Andrew J.; Fuller, Clifton D. (November 2023, INFORMS Journal on Computing)

   Chemotherapy drug administration is a complex problem that often requires expensive clinical trials to evaluate potential regimens; one way to alleviate this burden and better inform future trials is to build reliable models for drug administration. This paper presents a mixed-integer program for combination chemotherapy (utilization of multiple drugs) optimization that incorporates various important operational constraints and, besides dose and concentration limits, controls treatment toxicity based on its effect on the count of white blood cells. To address the uncertainty of tumor heterogeneity, we also propose chance constraints that guarantee reaching an operable tumor size with a high probability in a neoadjuvant setting. We present analytical results pertinent to the accuracy of the model in representing biological processes of chemotherapy and establish its potential for clinical applications through a numerical study of breast cancer. History: Accepted by Paul Brooks, Area Editor for Applications in Biology, Medicine, & Healthcare. Funding: This work was supported by the National Science Foundation [Grants CMMI-1933369 and CMMI-1933373]. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.0207 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2022.0207 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ . 

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