Dr. Hyun A Lee attended the SimCYP workshop on model-informed drug development, held on November 12th - 15th, 2019, in Shanghai, China. The SimCYP simulator is a platform for modeling and simulation of physiologically-based pharmacokinetics (PBPK) and pharmacodynamics in virtual humans and laboratory animals. It is one of the most sophisticated solutions for assisting in dose selection and informing product labeling. At CCADD, the SimCYP simulator has been used for physiologically-based pharmacokinetic and pharmacodynamic modeling and simulation of test articles under preclinical and clinical development.

Th workshop offered an in-dept insight into specific areas of PBPK modeling such as transporter-related absorption, distribution, metabolism, excretion, and toxicity (ADMET) and complex drug-drug interactions (DDIs). The workshop courses consisted of lectures and hands-on practical sessions tutored by the SimCYP simulator experts. Dr. Hyun A Lee learned good practices in combining data from both in vitro and clinical studies, while gaining experiences in using such data within physiologically-based pharmacodynamic models to evaluate the DDI liability of drug candidates. She also gained insights into mechanistic approaches to predict the impact of drug transport proteins on ADMET. For those who are interested in the SimCYP workshop's materials, please contact her. 

The 2019 fall conference of The Korean Society of Medical Informatics (KOSMI), organized by Kyungpook National University Hospital (KNUH), was held November 8-9, 2019, at the Global Plaza, Kyunpook National University, Daegu. Prof. Howard Lee, Yoomin Jeon and Junsik Moon participated in the conference.

The conference presented 19 symposia, 6 oral presentation sessions of pre-selected paper submissions, and 3 tutorials in healthcare information, pharmaceutical and big data research which focused on analysis, application and standardization of data based on artificial intelligence (AI) and machine learning. Sharing research ideas and analysis techniques, the attendees had an in-depth discussion on emerging issues and utilization in the fields of medical informatics.

On the second day, Prof. Lee chaired one of the oral presentation sessions entitled "New Drug and Pharmacovigilance", where he stressed full understanding of the research domain by communicating with experts in each research field. On the other hand, Yoomin presented two posters titled 'A Dimensionality Reduction Model to Increase the Efficiency and Accuracy of Clinical Trial Feasibility Assessment Using Electronic Medical Records' and 'A CDM-based Clinical Trial to Evaluate the Efficacy and Safety of SGLT2 Inhibitors as Add-on Treatment in Patients with Type 2 Diabetes Mellitus on Metformin, Sulfonylurea and/or DPP-4 Inhibitors'. Yoomin's poster presentations were well received.

Through the conference, the three members of CCADD were delighted to get introduced to the leading academicians and industry experts in the field of medical informatics. Furthermore, Prof. Lee and two CCADD members had a fun discussion that helped them look deeply into their current activities and direction of future research. Their collected insights out of the conference will be further discussed at the upcoming year-end workshop in early December.

The fifth annual Observational Health Data Sciences and Informatics (OHDSI) Symposium was held on September 15-17, 2019. OHDSI is a multi-stakeholder community on a journey to develop reliable real-world evidence through methodological research and open-source analytics development to bring out the value of observational health data. This year, more than 400 attendees gathered in North Bethesda, Maryland for the symposium. Around 70 participants flew in from Korea, including Prof. Howard Lee and Yoomin Jeon. The symposium had 1 day packed with dynamic and engaging keynote lectures, panel discussions, and a collaborator showcase featuring 7 lightning talks, 10 interactive demonstrations of OHDSI's open-source software, and nearly 80 poster presentations. The other 2 days of the symposium offered more practical hands-on tutorial workshops covering 6 different topics related to real-world data. The tutorial sessions covered the following topics: 1) OMOP Common Data Model & Standardized Vocabularies, 2) Cohort Definition/Phenotyping, 3) Patient-Level Prediction (PLP), 4) Population-Level Estimation (PLE), 5) Data Quality, 6) Extraction, Transformation, and Load process (ETL). Through these hands-on tutorial sessions, Prof. Lee and Yoomin were able to better understand how to leverage the ATLAS, a type of OHDSI's open-source software for designing and executing analytical use cases for clinical characterization, PLP, and PLE within one institution or across the entire OHDSI network. All the tutorial materials can be found here!

As a part of the OHDSI's knowledge-sharing mission, the Book of OHDSI was officially released and distributed for free at the symposium. The book is 470 pages long, consists of twenty chapters in 5 different sections: the OHDSI Community, Uniform Data Representation, Data Analytics, Evidence Quality, and OHDSI Studies. Many OHDSI community members voluntarily chipped-in to summarize all the knowledge developed over its existence into one place, which will assist both newcomers and data science veterans in doing research related to common data model. The book is available on Amazon or online for free. 

Hyun A Lee, a doctoral candidate at CCADD, attended the 28th Population Approach Group in Europe (PAGE)'s annual meeting, held on June 11th - 14th, 2019, in Stockholm, Sweden. PAGE represents a community with a shared interest in data analysis using the population approach for better-informed model-driven drug development. Although PAGE is based in Europe, the community is comprised of people from around the world. PAGE has been in existence since 1992, and its membership exceeds 500. The goal of the PAGE meeting is to bring together individuals who share the passion to learn, train, and use model-based population approach methods for data analysis in drug development. 

This year's keynote lecture was on the use of pharmacometrics in vaccine discovery and development by Dr. Jeff Sachs, Merck, who introduced the audience to several examples of pharmacometric applications across decisions impacted and methods used (e.g., applications of modeling and simulation that supported both go and no-go decisions, and increased power in trial design while saving considerable cost by optimizing sampling of subjects' disease state, and an application of modeling and simulation providing a novel phase 3 endpoint substantially increasing power of a proposed trial design). Dr. Nicky Best, GlaxoSmithKline, gave a tutorial on the use of informative priors in model-based drug development, where she talked about how informative priors are elicited from experts, or constructed from historical data, and how such priors could be implemented in models to inform different stages of drug development. Additionally, there were 25 invited lectures/presentations and >300 posters, tutorials, pre- and post-meeting workshops, coupled with abundant networking opportunities with attendees from a different part of the world. 

Hyun A presented a poster at the meeting that detailed the development of a pharmacokinetic/pharmacodynamic (PK/PD) model of YH4808, a novel potassium-competitive acid blocker to treat gastric acid related disease. In this study, the mutual relationships between the plasma concentrations of YH4808 and the time course of intragastric pH after single and multiple oral administration with YH4808 in humans were quantitatively evaluated using a PK/PD model. For those who are interested in Hyun A's research work, please contact her. 

Prof. Howard Lee proposed health insurance reimbursement for the combination therapy of DPP4 inhibitors and SGLT2 inhibitors, irrespective of their labels as approved by the Korea Ministry Food and Drug Safety (MFDS), at a special session organized by the Korean Diabetes Association (KDA), in association with its Spring Conference 2019, held on May 9-11, 2019, at the HICO, Kyeongju, Korea. Unlike other countries including the USA, EU, and Japan, MFDS in Korea has approved the combination therapy of SGLT2 inhibitors with other oral hypoglycemic agents, particularly with DPP4 inhibitors, only on the basis individual drugs, not on the therapeutic class. This unique regulatory approval has contributed to the delayed reimbursement of various combination therapies involving SGLT2 inhibitors since their approvals. 

The delayed reimbursement has caused a lot of debates not only between the pharmaceutical industry and the Health Insurance Review and Assessment Service or HIRA, but also among clinicians. With this background, the KDA asked Prof. Lee to share his perspectives from the points of drug regulatory science if the reimbursement for the combination therapy of DPP4 inhibitors and SGLT2 inhibitors on the basis of therapeutic class, not on the individual drug, has any scientific and clinical rationale. Prof. Lee, based on an intensive systematic literature review focusing on the pharmacokinetics, drug-drug interactions, clinical efficacy, and safety profiles of the combination treatment with DPP4 inhibitors and SGLT2 inhibitors, discussed that it is highly unlikely any combination of the two classes would interact in a clinically meaningful and significant way. Furthermore, Prof. Lee argued that it is very likely for every combination of a DPP4 inhibitor with an SGLT2 inhibitor to result in an additional, significant, and clinically meaningful decrease in HbA1c or glycated hemoglobin. However, since not every combination has been studied for its safety profiles although it is likely to be similar to those of monotherapy, Prof. Lee proposed to perform a real world data study under the auspice of KDA, sponsored by the pharmaceutical industry, to explore and confirm the safety and efficacy profiles of the combination therapy.      

Reflecting the interest in the reimbursement issue, the conference room was full of clinicians, industry representative, and journalists even though the session was presented early in the morning on Saturday. More detailed information on the session can be found here. 

On December 20, 2018, CCADD had a day-long workshop at the Yeongeon Campus. The workshop was attended not only by the existing CCADD members, but also by a new CCADD intern and a graduate student in the Interdisciplinary Program of Clinical Pharmacology at Seoul National University. The workshop included 12 presentations, the theme of which covered the history and milestones of CCADD, educational and research activities, talent acquiring strategy, homepage management, student internship experiences, communication, and teambuilding exercise. Furthermore, Professor Kyung-Sang Yu from the SNU College of Medicine and SNU Hospital (Department of Clinical Pharmacology) was invited to a special lecture session. Prof. Yu talked about the importance of e-mail as a means of business communication. He also stressed the appropriate e-mail manners in various business communication contexts.

After the workshop, CCADD members and their family members or invited friends went on a year-end dinner party, which was extended to a sleepover program. All brought a so-called 'useless' gift to the party, which as real fun. The winner of the most useless gift was Tae Chung, who received a used book named 'Sleep 2', written by Bernard Werber, but without having its first book, i.e., 'Sleep1'.

Okay, let's now look at the pictures below and you will easily notice how crazy the party was!

Prof. Howard Lee and Yoomin Jeon attended the 2018 Conference on Empirical Methods in Natural Language Processing (EMNLP 2018) held at the Square Meeting Center in Brussels from October 31^st through November 4^th, 2018. EMNLP is one of the top-tier conferences in the area of natural language processing organized by SIGDAT, the Association for Computational Linguistics (ACL) special interest group on linguistic data and corpus-based approaches to NLP. With the current artificial intelligence and machine learning boom from a variety of disciplines, this year's conference had a record-breaking number of submissions (2,231) and 2,500+ attendees, a 48% increase compared with EMNLP 2017. Of all the long and short papers submitted, only 549 papers were accepted, which can be found in the EMNLP proceedings. The conference included two days of workshops, followed by three days of main conference sessions including long and short presentations, tutorials, and demos. Researchers and practitioners from around the world gathered to share their latest research findings and emerging trends in machine learning for NLP, machine translation, language models, text mining, information extraction, and many more. 

In the 'Writing Code for NLP Research' tutorial, researchers from Allen AI Institute shared their best practices learned from designing the development of the Allen NLP toolkit, a PyTorch-based open-source library for deep learning NLP research. It was an excellent tutorial to learn practical advice on writing research code and to recognize the importance of having good quality codes. In the 'Deep Latent Variable Models of Natural Language' tutorial, deep latent variable models were covered, which are emerging as a useful tool in NLP applications. Mainly, three types of latent variable models (discrete, continuous, and structured) and inference strategies (exact gradient, sampling, and conjugacy) over the latent variables were examined. 

There were a number of presentations/papers in the clinical domain. One of the interesting papers, titled 'emrQA: A Large Corpus for Question Answering on Electronic Medical Records', proposed a novel semi-automated framework to generate domain-specific large-scale question answering (QA) corpus by leveraging expert annotations on clinical notes for various NLP tasks from the i2b2 challenge datasets. For medical QA on EMR, they released 400K+ question-answer evidence pairs and 1M question-logical forms, a representation useful for generating corpus. Generating patient-specific QA from an EMR is an important NLP task to process a natural language question and provide a human level accuracy answer. Among many datasets that were presented at the conference, a clinical domain dataset MedNLI was included. MedNLI is a Natural Language Inference (NLI) dataset on the medical history of patients annotated by physicians, which we can later refer in our research.   

Prof. Howard Lee and Hyun A Lee attended the 9^th American Conference on Pharmacometrics (ACoP9), held October 7^th to 10^th, 2018, at the Loews Coronado Bay Resort near San Diego, CA, USA. ACoP is the annual scientific meeting of the International Society of Pharmacometrics (ISoP), an organization comprised individuals from around the globe from various backgrounds in pharmaceutics, engineering, statistics, and mathematics, who are passionate about advancing and promoting the field of pharmacometrics. The theme of ACoP9, "Modeling without Bounds",  means "internationalization/collaboration" and "fusion/integration" of pharmacometrics groups, methods, and tools among the fields of pharmacometrics and systems pharmacology, with more than 1,000 members from over 30 countries. Consistent with this theme, inspiring and innovative talks by the Keynote (Mr. Walter Woltosz, Simulations Plus) and the State of Art ( Prof. Andrew Lo, Massachusetts Institute of Technology) speakers were presented. The titles of their speeches were "Rocket motors, Stephen Hawking, and drug development" and "p-Values vs. Patient values: An Analytic Perspective", respectively. In addition, the pre-conference program on "Digital Health Technology, Machine Learning and Artificial Intelligence: The Future of Clinical Trials and Informative Therapeutic Decisions?" highlighted the latest innovations and clinical applications of digital health technologies. The conference program included >100 invited lectures/presentations and over 300 posters, tutorials, pre- and post-meeting workshops, and abundant networking opportunities with attendees from around the world. 

Hyun A Lee presented a poster at the meeting that detailed the development of a physiologically based pharmacokinetic (PBPK) model of YH4808, a novel potassium-competitive acid blocker to treat gastric acid related disease. In this study, the mechanistic cause of the decreased exposure YH4808 after multiple oral administration particularly at higher doses could be identified using the PBPK model.

In addition, you may want to contact Hyun A for her poster.