Optimization of storage and picking systems in warehouses

La croissance du commerce électronique exige une hausse des performances des systèmes d'entreposage, qui sont maintenant repensés pour faire face à un volume massif de demandes à être satisfait le plus rapidement possible. Le système manuel et le système à robots mobile (SRM) sont parmi les plus utilisés pour ces activités. Le premier est un système centré sur l'humain pour réaliser des opérations complexes que les robots actuels ne peuvent pas effectuer. Cependant, les nouvelles générations de robots autonomes mènent à un remplacement progressif par le dernier pour augmenter la productivité. Quel que soit le système utilisé, plusieurs problèmes interdépendants doivent être résolus pour avoir des processus de stockage et de prélèvement efficaces. Les problèmes de stockage concernent les décisions d'où stocker les produits dans l'entrepôt. Les problèmes de prélèvement incluent le regroupement des commandes à exécuter ensemble et les itinéraires que les cueilleurs et les robots doivent suivre pour récupérer les produits demandés. Dans le système manuel, ces problèmes sont traditionnellement résolus à l'aide de politiques simples que les préparateurs peuvent facilement suivre. Malgré l'utilisation de robots, la même stratégie de solution est répliquée aux problèmes équivalents trouvés dans le SRM. Dans cette recherche, nous étudions les problèmes de stockage et de prélèvement rencontrés lors de la conception du système manuel et du SRM. Nous développons des outils d'optimisation pour aider à la prise de décision pour mettre en place leurs processus, en améliorant les mesures de performance typiques de ces systèmes. Certains problèmes traditionnels sont résolus avec des techniques améliorées, tandis que d'autres sont intégrés pour être résolus ensemble au lieu d'optimiser chaque sous-système de manière indépendante. Nous considérons d'abord un système manuel avec un ensemble connu de commandes et intégrons les décisions de stockage et de routage. Le problème intégré et certaines variantes tenant compte des politiques de routage communes sont modélisés mathématiquement. Une métaheuristique générale de recherche de voisinage variable est présentée pour traiter des instances de taille réelle. Des expériences attestent de l'efficience de la métaheuristique proposée par rapport aux modèles exacts et aux politiques de stockage communes. Lorsque les demandes futures sont incertaines, il est courant d'utiliser une stratégie de zonage qui divise la zone de stockage en zones et attribue les produits les plus demandés aux meilleures zones. Les tailles des zones sont à déterminer. Généralement, des dimensions arbitraires sont choisies, mais elles ignorent les caractéristiques de l'entrepôt et des demandes. Nous abordons le problème de dimensionnement des zones pour déterminer quels facteurs sont pertinents pour choisir de meilleures tailles de zone. Les données générées à partir de simulations exhaustives sont utilisées pour trainer quatre modèles de régression d'apprentissage automatique - moindres carrés ordinaire, arbre de régression, forêt aléatoire et perceptron multicouche - afin de prédire les dimensions optimales des zones en fonction de l'ensemble de facteurs pertinents identifiés. Nous montrons que tous les modèles entraînés suggèrent des dimensions sur mesure des zones qui performent meilleur que les dimensions arbitraires couramment utilisées. Une autre approche pour résoudre les problèmes de stockage pour le système manuel et pour le SRM considère les corrélations entre les produits. L'idée est que les produits régulièrement demandés ensemble doivent être stockés près pour réduire les coûts de routage. Cette politique de stockage peut être modélisée comme une variante du problème d'affectation quadratique (PAQ). Le PAQ est un problème combinatoire traditionnel et l'un des plus difficiles à résoudre. Nous examinons les variantes les plus connues du PAQ et développons une puissante métaheuristique itérative de recherche tabou mémétique en parallèle capable de les résoudre. La métaheuristique proposée s'avère être parmi les plus performantes pour le PAQ et surpasse considérablement l'état de l'art pour ses variantes. Les SRM permettent de repositionner facilement les pods d'inventaire pendant les opérations, ce qui peut conduire à un processus de prélèvement plus économe en énergie. Nous intégrons les décisions de repositionnement des pods à l'attribution des commandes et à la sélection des pods à l'aide d'une stratégie de prélèvement par vague. Les pods sont réorganisés en tenant compte du moment et de l'endroit où ils devraient être demandés au futur. Nous résolvons ce problème en utilisant la programmation stochastique en tenant compte de l'incertitude sur les demandes futures et suggérons une matheuristique de recherche locale pour résoudre des instances de taille réelle. Nous montrons que notre schéma d'approximation moyenne de l'échantillon est efficace pour simuler les demandes futures puisque nos méthodes améliorent les solutions trouvées lorsque les vagues sont planifiées sans tenir compte de l'avenir. Cette thèse est structurée comme suit. Après un chapitre d'introduction, nous présentons une revue de la littérature sur le système manuel et le SRM, et les décisions communes prises pour mettre en place leurs processus de stockage et de prélèvement. Les quatre chapitres suivants détaillent les études pour le problème de stockage et de routage intégré, le problème de dimensionnement des zones, le PAQ et le problème de repositionnement de pod. Nos conclusions sont résumées dans le dernier chapitre.The rising of e-commerce is demanding an increase in the performance of warehousing systems, which are being redesigned to deal with a mass volume of demands to be fulfilled as fast as possible. The manual system and the robotic mobile fulfillment system (RMFS) are among the most commonly used for these activities. The former is a human-centered system that handles complex operations that current robots cannot perform. However, newer generations of autonomous robots are leading to a gradual replacement by the latter to increase productivity. Regardless of the system used, several interdependent problems have to be solved to have efficient storage and picking processes. Storage problems concern decisions on where to store products within the warehouse. Picking problems include the batching of orders to be fulfilled together and the routes the pickers and robots should follow to retrieve the products demanded. In the manual system, these problems are traditionally solved using simple policies that pickers can easily follow. Despite using robots, the same solution strategy is being replicated to the equivalent problems found in the RMFS. In this research, we investigate storage and picking problems faced when designing manual and RMFS warehouses. We develop optimization tools to help in the decision-making process to set up their processes and improve typical performance measures considered in these systems. Some classic problems are solved with improved techniques, while others are integrated to be solved together instead of optimizing each subsystem sequentially. We first consider a manual system with a known set of orders and integrate storage and routing decisions. The integrated problem and some variants considering common routing policies are modeled mathematically. A general variable neighborhood search metaheuristic is presented to deal with real-size instances. Computational experiments attest to the effectiveness of the metaheuristic proposed compared to the exact models and common storage policies. When future demands are uncertain, it is common to use a zoning strategy to divide the storage area into zones and assign the most-demanded products to the best zones. Zone sizes are to be determined. Commonly, arbitrary sizes are chosen, which ignore the characteristics of the warehouse and the demands. We approach the zone sizing problem to determine which factors are relevant to choosing better zone sizes. Data generated from exhaustive simulations are used to train four machine learning regression models - ordinary least squares, regression tree, random forest, and multilayer perceptron - to predict the optimal zone sizes given the set of relevant factors identified. We show that all trained models suggest tailor-made zone sizes with better picking performance than the arbitrary ones commonly used. Another approach to solving storage problems, both in the manual and RMFS, considers the correlations between products. The idea is that products constantly demanded together should be stored closer to reduce routing costs. This storage policy can be modeled as a quadratic assignment problem (QAP) variant. The QAP is a traditional combinatorial problem and one of the hardest to solve. We survey the most traditional QAP variants and develop a powerful parallel memetic iterated tabu search metaheuristic capable of solving them. The proposed metaheuristic is shown to be among the best performing ones for the QAP and significantly outperforms the state-of-the-art for its variants. The RMFS allows easy repositioning of inventory pods during operations that can lead to a more energy-efficient picking process. We integrate pod repositioning decisions with order assignment and pod selection using a wave picking strategy such that pods are parked after being requested considering when and where they are expected to be requested next. We solve this integrated problem using stochastic programming considering the uncertainty about future demands and suggest a local search matheuristic to solve real-size instances. We show that our sample average approximation scheme is effective to simulate future demands since our methods improve solutions found when waves are planned without considering the future demands. This thesis is structured as follows. After an introductory chapter, we present a literature review on the manual and RMFS, and common decisions made to set up their storage and picking processes. The next four chapters detail the studies for the integrated storage and routing problem, the zone sizing problem, the QAP, and the pod repositioning problem. Our findings are summarized in the last chapter

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

Background Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis. Methods PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850. Findings Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals. Interpretation Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function.</p