Advisor: Prof. Sabounchi Antibiotic Overuse Hamed Kianmehr Olivia Plante Advisor: Prof. Sabounchi Systems Science and Industrial Engineering Department State University of New York at Binghamton System Dynamics Colloquium Worcester Polytechnic Institute (WPI) – Spring 2016

Resistance and Antibiotic Use Problem: As antibiotics use and misuse increases ↑ , resistant strains are naturally selected  Leading to Diminishing AB efficacy, Higher dose requirements, and Death Sir Alexander Fleming discovered penicillin 1928 Penicillin was first used in soldiers in the 1940s Penicillin R-pneumococcus discovered in 1965 In 2010, over 7.3 billion standard units of penicillin were consumed worldwide http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/ http://www.medicalnewstoday.com/articles/216798.php Sir Alexander Fleming warned that its benefit might not last. Accepting the 1945 Nobel Prize in Medicine, he said: “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them… There is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.”

Causes Antibiotic Resistance has increased due to: Over prescription Lack of Diagnostic Accuracy Prescription Regimen Non-compliance Agricultural Use

The pipeline is drying up……. The same AB are prescribed over And over again New AB are reserved for last resort use Production has decreased due to: Inability to Recoup Costs of $1 billion trial Loss of Innovation (Creative Dry Spell) 10-15 years time from R&D to validation In 2004 for ex. There were only 5 new antibiotics comapared to 500 chronic disease drugs for which reistance is not an issue https://thefern.org/2013/11/imagining-the-post-antibiotics-future/ http://www.pewtrusts.org/en/research-and-analysis/issue-briefs/2014/03/12/tracking-the-pipeline-of-antibiotics-in-development In 2012, 6 on market BL, 2 in phase III, 2 in phase II, 1 in phase 1 In 2011, 0 in phase III,1 in phase II, 0 in phase 1

Pressure to Prescribe Patient expectations and demands are associated with irrational prescribing behavior and lack of evidence based practice Patients request RX based on advertisements direct-to-consumer Healthcare professionals are also under pressure from pharmaceutical companies to use their products Socioeconomic status, insurance status, educational status may also influence patients expectations as well as healthcare professional’s behavior http://www.ncbi.nlm.nih.gov/pubmed/21397877

Model System – AB Usage Rate Patient-Physician relationship in the healthcare system influences the prescribing habits and thus AB usage Some patients may enter the ER system directly or wait until their symptoms get worse Many patients don't comply or take un-prescribed meds

Reference Mode

Causal Loop Its simplified model of CLD

Simulation Results

Insights Antibiotic overuse is highly dependent on the infection rate As infections increase, AB use will increase and resistance will likely increase, leading to a need for a greater diversity of AB

Solutions Greater need to collect data in a global system and share insights Improve molecular data and diagnostics of individual patients (personalized medicine) Improve hygiene and quality control in the healthcare setting De-linkage of pharmaceutical R&D from production costs to increase the diversity of AB available to prescribers so that if AB use increases with population and infection rate, it will have less of an impact on the eventual resistance that accompanies the increase in AB usage Main recommendations A new business model needs to be developed in which the return on investment in R&D on antibiotics is delinked from the volume of sales. Increased public financing of a broad menu of incentives across the antibiotic life-cycle is required, targeted at encouraging the development of antibiotics to counter the greatest microbial threats. The assessment of current and future global threats arising from resistance should be updated periodically in order to identify which classes of product are a priority for incentives. The delinkage model should prioritize both access and conservation. Domestic expenditures on the model need to be globally coordinated, including through the establishment of a secretariat, and global participation in the model is the ultimate goal. Revenues for pharmaceutical companies need to be delinked from sales of antibiotics to avoid their over-use and avert a public health crisis - See more at: https://www.chathamhouse.org/publication/towards-new-global-business-model-antibiotics-delinking-revenues-sales#sthash.aop8jXA5.dpuf

Future Work Increase the validity of the model for real data trends in order to predict outcomes based on potential policy implementations Add more variables to enhance the reality of the dynamic problem such as behavioral surveys(physician prescribing habits and patients expectations) in addition to epidemiological data from the same area

Requests for Feedback What should be emphasized in the causal structure- agriculture, pharma production, AB usage, other…? How can we make it more accessible to a diverse range of stakeholders?