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. 

Prof. Howard Lee and Yoomin Jeon participated in the 2nd Korea Clinical Datathon, organized by the Korea National Enterprise for Clinical Trials (KoNECT), September 20-22, 2019. The event was well-attended, which brought over 200 participants, almost doubling the number of those who joined last year. A Datathon is a type of data-focused hackathons, where interdisciplinary teams are challenged to come up with analysis results using their creativity and data science skills within a limited amount of time. The Korea Clinical Datathon aims to bring together clinicians, data scientists, statisticians, students, and those with domain-specific knowledge to brainstorm ideas and to address real-world clinical challenges by applying data analytics technologies. Participants were given access to 3 types of datasets extracted from MIMIC-III (Medical Information Mart for Intensive Care-III), the Seoul National University Hospital VitalDB (vital signs database of surgical patients), and the Ajou University Hospital CDM (Common Data Model).

The first day kicked off with 14 different open-ended clinically relevant questions to address a variety of topics in the medical field. Prof. Lee and Yoomin were on Team 6, comprised of 13 members including four clinicians, three statisticians, one data scientist, and three students. Lead by Prof. Lee, Team 6 came up with the following research question: "Are add-on sodium-glucose cotransporter 2 inhibitors (SGLT2i) efficacious and safe in patients with type 2 diabetes mellitus who are on metformin, sulfonylurea and/or dipeptidylpeptidase-4 inhibitors (DPP4i)?". Using the Ajou University Hospital CDM real-world data, Team 6 has successfully shown that patients with type 2 diabetes mellitus can benefit from add-on SGLT2i treatment in terms of both additional efficacy and comparable safety. Based on the analysis, adding an SGLT2i has shown reductions in HbA1c (approximately 0.76%, very similar to previous publication results) and body weight. In addition, a higher risk of urinary tract and genital infections was found, which are the most common side effects identified with SGLT2i in clinical trials. 

On the last day, the sleep-deprived but exhilarated participants presented their findings for a competition. Even though Team 6 failed to win the competition, it was a unique opportunity to get hands-on experience and to learn about possibilities of how machine learning/statistics/data analytic skills can address current challenges in healthcare.

Jun Sik Moon has started a new research career in the Center for Convergence Approaches in Drug Development (CCADD) at the Graduate School of Convergence Science and Technology, Seoul National University, since October 1, 2019. Jun Sik was a researcher at the Department of Mathematics, Research & Business Development Foundation, Sogang University (2018-2019) shortly before he joined CCADD. As the research interests in CCADD have gradually expanded, including AI and machine learning in drug development, CCADD wants to acquire talents such as Jun Sik, who could bring CCADD mathematical skills. Please join us in warmly welcoming Jun Sik!

Jun Sik Moon was a researcher at the Graduate School of Convergence Science and Technology, Seoul National University. Jun Sik was a researcher at Department of Mathematics, Research & Business Development Foundation, Sogang University (2018-2019) shortly before he joined CCADD in October 2019. He received his master degree in mathematics at Sogang University (2010-2013) under the supervision of Prof. Jens Hoppe. During his master course, he studied the motion of particles and relationship between them on non-commutative space-time, one of the classical topics of mathematical physics.

Join us in congratulating Hyun A Lee for her successful graduation with a PhD degree in medical science in August 2019! Dr. Hyun A Lee came to CCADD in 2017, 2 years after she started pursuing a PhD degree under Prof. Howard Lee's supervision in association with the Graduate School of Convergence Science and Technology, Seoul National University. Dr. Lee is the first PhD student who has ever graduated from CCADD. The title of her thesis was "Mechanistic Physiologically based Pharmacokinetic/Pharmacodynamic Models to Evaluate the Mutual Relationship between an Acid Pump Antagonist and Intragastric pH in Humans (Using YH4808, a novel K⁺-competitive acid blocker, as an example)".

Dr. Lee will stay with CCADD at least an additional year as a BK21 Plus postdoctoral researcher. She will be performing research in the areas of physiologically-based pharmacokinetic modeling, pharmacokinetic/pharmacodynamics (PK/PD) modeling and simulation, and artificial intelligence-based PK/PD modeling and simulation in clinical drug development. 

The In Depth 60 Minutes, an investigative journalism program broadcast by KBS, featured an interview with Prof. Howard Lee on August 16, 2019 with respect the recent Invossa debacle. Invossa is a gene and cell therapy approved to treat patients with osteoarthritis of the knee. Invossa was claimed to contain genetically transformed chondrocytes, which turned out not to be the case. Instead, they were cells originated from the human embryonic kidney, which could cause cancer to develop in those who received Invossa. Invossa has been administered to more than 3,000 patients only in Korea. The Korea Ministry of Food and Drug Safety (MFDS) revoked the marketing approval of Invossa, and promised to initiate a nationwide pharmacovigilance program to investigate the safety impact of Invossa, which though has not been in effect yet. 

In the show, Prof. Lee emphasized why misbranding or mislabelling is a significant health harm, which can be legally penalized. Furthermore, he explained why MFDS was not able to detect what went wrong in the case of approval of Invossa. Prof. Lee added, "Although MFDS has been trying to renovate themselves over the past decade or so, it still lacks the expertise and manpower required to adequately review the safety and efficacy of the drug, particularly advanced therapies such as Invossa." Prof. Lee was featured in a total of four clips. 

The full program can be watched by clicking here.

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. 

Two senior undergraduate students, Yonghan Kwon and Won Jeong Go, joined CCADD for the summer internship program on July 1, 2019, which will end in eight weeks.

Yonghan has studied applied statistics and taken several data mining and machine learning classes at Kyonggi University. Being familiar with R and Python, Yonghan wants to improve his coding/programming skills by participating in several CCADD's ongoing AI projects awarded by the National Institute of Food Drug Safety Evaluation (NIFDS) and South Korean Ministry of Trade, Industry, and Energy (MOTIE).

Won Jeong has studied at Handong University with a major in life science and a minor in computer science. Won Jung's research interests include genomic analysis for the safe use of drugs, and is happy to work with Dr. Jeong-An Gim in the pharmacoepigenomic study of tacrolimus. She hopes to learn essential concepts necessary for the analysis of genomic data using computational techniques.

CCADD welcomes Yonghan and Won Jeong, and hopes them to enjoy the rest of their internship programs.

CCADD has been recently awarded a new research grant from the South Korean Ministry of Trade, Industry, and Energy (MOTIE) to develop a clinical trial simulation system. The kick-off meeting was held on June 3, 2019. The total research funding was 1.4 billion Korean Won, which is equivalent to $1,200,000. The three-year project will be led by Mr. Charles Joochul Lee, a general manager of Selvas AI Inc, and CCADD (PI: Prof. Howard Lee) will develop a CDM-based simulation system, by which clinical trial feasibility is performed. In the process, CCADD will also design a user-friendly interface for the system. 

The title of the proposed research plan is the 'Smart User-friendly CDM-based Clinical trial dEsign Support System, or SUCCESS', an interesting term coined by Prof. Howard Lee, which symbolizes the desire for success in clinical drug development.  

Prof. Howard Lee was invited to the 2019 annual congress of the European Association for Clinical Pharmacology and Therapeutics or EACPT2019, held on June 29 - July 2, in Stockholm, Sweden. Prof. Lee gave an overview of the current polypharmacy status in Korea. Polypharmacy, commonly defined as prescribing 6 or more drugs concomitantly on a single prescription, can make patients vulnerable to adverse drug reactions caused by drug interactions. Furthermore, polypharmacy can undermine the financial wellness of the health insurance system. 

In Korea, the proportion of polypharmacy has decreased from 65.8% in early 2000 to 43.7% in 2013. However, polypharmacy is still a big health issue in Korea, particularly in younger children (1-9 years) and the elderly. Likewise, low income is strongly associated with polypharmacy in the elderly in Korea. Currently, there is no national guideline or measure implemented to curb polypharmacy in Korea. Therefore, policies and nationwide efforts, along with educational campaigns for not only patients, but physicians, led by clinical pharmacology professionals, are to be put into practice to keep patients from unwanted health problems caused by polypharmacy and to promote optimal drug therapy. Prof. Lee's talk was well received, followed by an interesting session of discussion at the meeting. A physician in the audience asked why polypharmacy is most common in early childhood in Korea, and Prof. Lee replied, "Prescribing antibiotics and other common cold medications is the major culprit."

The reception for EACPT2019 took place at the Golden Hall, Stockholm City Center. This hall is the place for the ball after the annual Nobel Banquet in the Blue Hall at the City Center. Below are a couple of photos taken at the reception with other Korean participants.