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. 

We cannot believe how quickly time has passed. CCADD students have finished the 15-week 'Clinical Pharmacokinetics and Pharmacodynamics in Drug Development' course with no leftovers or dropouts. The students have learned in details how the core principles and concepts of pharmacokinetics and pharmacodynamics could be applied to speed up clinical drug development and to increase its efficiency, particularly for anti-cancer drugs. In the class, students have not only thoroughly reviewed two textbooks ('Pharmacokinetics in Drug Development, Volume 3 and 4') from chapter to chapter, but also studied other literature, which could go up to tens of published papers. Tae, one of the students who took the course, said, "It was eye-opening to see how what we studied in clinical pharmacokinetics and pharmacodynamics has been used to real world drug development." He added, "The class was also full of fun. It was an opportunity for the CCADD students to know each other better."

This course was taught in English. That means all the student presentations were given in English!

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 April 24, 2019, Prof. Howard Lee and 5 CCADD members presented a seminar at the Laboratory of Genome Epidemiology and Health Big Data (G-Epi), Graduate School of Public Health at Seoul National University. It was a return visit in response to G-Epi's one 10 months ago. G-Epi (PI: Joohon Sung) focuses on the data analysis of genetic, demographic, physiological, and environmental factors of complex diseases. G-Epi uses epidemiological, statistical, and bioinformatics approaches to analyze large-scale omics data.

In the seminar, Prof. Howard Lee introduced G-Epi to one of the CCADD's current Artificial Intelligence (AI) research projects, entitled 'A dimensionality reduction model to increase the efficacy and accuracy of clinical trial feasibility assessment using electronic medical records.' Hyun A Lee and Dr. Jeong-An Kim also spoke about their research projects, a PBPK modeling analysis of an acid-reducing agent under clinical development and a pharmacoepigenomic analysis of Tacrolimus, respectively. The seminar was a great opportunity for both labs to share their research experiences, ideas, and future perspectives. G-Epi and CCADD are looking forward to closely working together in various research projects in the future. 

ACTRiS or the AI-based Clinical Trial Resource Information System is one of the CCADD’s recent research projects, which was successfully completed by early 2019. On January 9, KIPO or the Korea Intellecutal Property Office granted a trademark registration for ACTRiS. This is a little, but meaningful success for those who have been actively involved in the design, plan, conduct, and completion of the ACTRiS research project, which include, but are not limited to, CCADD members, Prof. Joon Sik Lee and his UX lab, Prof. Jin Wook Choi and his medical informatics lab, Prof. Jang Hee Hong and his Pharmacogenetics lab, Prof. Hyoun-Joong Kong, Mebixon, and, lastly, but not the least, Selvas AI.

CCADD has also filed the logos for P-MATCH and ACTRiS for registration with KIPO. 

Prof. Howard Lee was invited to speak at an educational seminar and an international symposium, both sponsored by the Pharmaceutical Society of Korea, in association of its spring convention, held in the Millennium Hilton Seoul, Korea, on April 25-26. The PSK is an academic organization representing pharmacy since its foundation in 1946, which has grown into the biggest institution for pharmacists in Korea. In the educational seminar, Prof. Lee talked about how bio-big data can be used for the efficient planning and conduct of clinical drug development. His talk was based on his experience and lessons learned in the two recent research projects that CCADD led and will be actively participating, i.e., ACTRiS and SUCCESS. His presentation has received media attention as summarized in a newspaper article.   

The international symposium was held on the second day of the convention. Prof. Lee introduced the audience to several possible applications of artificial intelligence (AI) to clinical trials, with a special focus on a CCADD research project using feature selection for clinical trial feasibility. This symposium was organized by Prof. Hwi-yeol Yun, Chungnam National University College of Pharmacy, a long-time friend and collaborator of Prof. Lee's.