A multi-objective production planning problem with the consideration of time and cost in clinical trials

Abstract Under increasingly challenging circumstances, pharmaceutical companies try to reduce the overproduction of clinical drugs, which is commonly seen in the pharmaceutical industry. When the overproduction is simply reduced without an efficient coordination of the inventories in the supply chain, the stock-outs at clinical sites and clinical trial delay can hardly be avoided. In this study, we propose a multi-objective model to optimize the production quantity, where the clinical trial duration and the total production and operational costs are minimized. The problem is formulated as a multi-stage stochastic programming model to capture the dynamic inventory allocation process in the supply chains. Since this problem's solving time and required memory can increase significantly with the increase of the stage and scenario numbers, the progressive hedging algorithm is applied as the solution approach in this paper. In the numerical experiments, we study this algorithm's performance and compare the solving efficiency with the direct solution approach. In addition, we identify the optimal production quantity of clinical drugs and give a discussion about the tradeoffs between the clinical trial delay and total cost.

[1]  Christian Prins,et al.  Fast heuristics for a combined production planning and vehicle routing problem , 2008 .

[2]  Jun Zhang,et al.  Transshipment and Its Impact on Supply Chain Members' Performance , 2005, Manag. Sci..

[3]  Gintaras V. Reklaitis,et al.  Integrated Planning and Optimization of Clinical Trial Supply Chain System with Risk Pooling , 2012 .

[4]  Ruud H. Teunter,et al.  Inventory models with lateral transshipments: A review , 2011, Eur. J. Oper. Res..

[5]  John R. Birge,et al.  Decomposition and Partitioning Methods for Multistage Stochastic Linear Programs , 1985, Oper. Res..

[6]  Yao Zhao,et al.  Planning for demand failure: A dynamic lot size model for clinical trial supply chains , 2011, Eur. J. Oper. Res..

[7]  Jasbir S. Arora,et al.  Survey of multi-objective optimization methods for engineering , 2004 .

[8]  David L. Woodruff,et al.  Progressive hedging and tabu search applied to mixed integer (0,1) multistage stochastic programming , 1996, J. Heuristics.

[9]  Yale T. Herer,et al.  Optimal and heuristic algorithms for the multi-location dynamic transshipment problem with fixed transshipment costs , 2003 .

[10]  David L. Woodruff,et al.  Progressive hedging innovations for a class of stochastic mixed-integer resource allocation problems , 2011, Comput. Manag. Sci..

[11]  Anthony Clemento New and Integrated Approaches to Successful Accelerated Drug Development , 1999 .

[12]  Hanif D. Sherali,et al.  A modification of Benders' decomposition algorithm for discrete subproblems: An approach for stochastic programs with integer recourse , 2002, J. Glob. Optim..

[13]  Henry G. Grabowski,et al.  Effective patent life in pharmaceuticals , 2000, Int. J. Technol. Manag..

[14]  Jinwoo Park,et al.  A combined model of network design and production/distribution planning for a supply network , 2002 .

[15]  Adam J. Fleischhacker,et al.  Positioning Inventory in Clinical Trial Supply Chains , 2015 .

[16]  Changzheng Liu,et al.  Solving Stochastic Transportation Network Protection Problems Using the Progressive Hedging-based Method , 2010 .

[17]  Ş. Tarim,et al.  The cost of using stationary inventory policies when demand is non-stationary , 2011 .

[18]  B. Beamon Supply chain design and analysis:: Models and methods , 1998 .

[19]  John M. Mulvey,et al.  Applying the progressive hedging algorithm to stochastic generalized networks , 1991, Ann. Oper. Res..

[20]  Y. Herer,et al.  Lateral stock transshipments in a two-location inventory system with fixed and joint replenishment costs , 1999 .

[21]  J.M. Laínez,et al.  Challenges and opportunities in enterprise-wide optimization in the pharmaceutical industry , 2012, Comput. Chem. Eng..

[22]  Keely L. Croxton,et al.  INVENTORY CONSIDERATIONS IN NETWORK DESIGN , 2005 .

[23]  M. Tzur,et al.  The dynamic transshipment problem , 2001 .

[24]  Josefa Mula,et al.  Mathematical programming models for supply chain production and transport planning , 2010, Eur. J. Oper. Res..

[25]  David L. Woodruff,et al.  Hashing vectors for tabu search , 1993, Ann. Oper. Res..

[26]  Nils Rudi,et al.  Who Benefits from Transshipment? Exogenous vs. Endogenous Wholesale Prices , 2004, Manag. Sci..

[27]  R. W. Hansen,et al.  The price of innovation: new estimates of drug development costs. , 2003, Journal of health economics.

[28]  Jørgen Tind,et al.  L-shaped decomposition of two-stage stochastic programs with integer recourse , 1998, Math. Program..

[29]  Lazaros G. Papageorgiou,et al.  An Aggregation Approach for Capacity Planning under Uncertainty for the Pharmaceutical Industry , 2003 .

[30]  Gintaras V. Reklaitis,et al.  Simulation-optimization approach to clinical trial supply chain management with demand scenario forecast , 2012, Comput. Chem. Eng..

[31]  Alexander Shapiro,et al.  Lectures on Stochastic Programming: Modeling and Theory , 2009 .

[32]  S. Dauzere-Peres,et al.  Integrated optimization of production and distribution for several products , 2006, 2006 International Conference on Service Systems and Service Management.

[33]  Marc Goetschalckx,et al.  Strategic production-distribution models: A critical review with emphasis on global supply chain models , 1997 .

[34]  Adam J. Fleischhacker AN INVESTIGATION OF CLINICAL TRIAL SUPPLY CHAINS , 2009 .

[35]  John R. Birge,et al.  Introduction to Stochastic Programming , 1997 .

[36]  Young Hae Lee,et al.  Production-distribution planning in supply chain considering capacity constraints , 2002 .

[37]  Nils Rudi,et al.  A Two-Location Inventory Model with Transshipment and Local Decision Making , 2001, Manag. Sci..

[38]  Benoit David,et al.  Balancing Risk and Costs to Optimize the Clinical Supply Chain—A Step Beyond Simulation , 2009, Journal of Pharmaceutical Innovation.

[39]  Asoo J. Vakharia,et al.  Integrated production/distribution planning in supply chains: An invited review , 1999, Eur. J. Oper. Res..

[40]  Costas D. Maranas,et al.  Managing demand uncertainty in supply chain planning , 2003, Comput. Chem. Eng..

[41]  David L. Woodruff,et al.  Obtaining lower bounds from the progressive hedging algorithm for stochastic mixed-integer programs , 2016, Math. Program..

[42]  R. Tyrrell Rockafellar,et al.  Scenarios and Policy Aggregation in Optimization Under Uncertainty , 1991, Math. Oper. Res..

[43]  Marshall L. Fisher,et al.  Coordination of production and distribution planning , 1994 .

[44]  Nilay Shah,et al.  Pharmaceutical supply chains: key issues and strategies for optimisation , 2004, Comput. Chem. Eng..

[45]  S. Sen Algorithms for Stochastic Mixed-Integer Programming Models , 2005 .

[46]  Herbert E. Scarf,et al.  Optimal Policies for a Multi-Echelon Inventory Problem , 1960, Manag. Sci..

[47]  David L. Woodruff,et al.  Toward scalable, parallel progressive hedging for stochastic unit commitment , 2013, 2013 IEEE Power & Energy Society General Meeting.

[48]  Thomas J Lynch,et al.  The phase III trial in the era of targeted therapy: unraveling the "go or no go" decision. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[49]  Paul I. Barton,et al.  Capacity Planning under Clinical Trials Uncertainty in Continuous Pharmaceutical Manufacturing, 1: Mathematical Framework , 2012 .

[50]  Adam J. Fleischhacker,et al.  Balancing learning and economies of scale for adaptive clinical trials , 2013 .

[51]  Lawrence W. Robinson,et al.  Optimal and Approximate Policies in Multiperiod, Multilocation Inventory Models with Transshipments , 1990, Oper. Res..

[52]  Kai Huang,et al.  Multi-stage Stochastic Programming Models in Production Planning , 2005 .

[53]  J. DiMasi,et al.  Pharmaceutical Innovation in the 21st Century: New Drug Approvals in the First Decade, 2000–2009 , 2011, Clinical pharmacology and therapeutics.

[54]  Jian Yang,et al.  Capacitated Production Control with Virtual Lateral Transshipments , 2007, Oper. Res..