Five CCADD members (Prof. Howard Lee, Dr. Soohyun Kim, Yoomin Jeon, Tae Chung, Serin Lee) have attended the Fall conference of The Korean Society of Medical Informatics (KOSMI) held at Chonbuk National University on November 22-23, 2018. The theme of the conference was 'Real World Data to optimize clinical trials', which reflects a growing role and value of big data and artificial intelligence for clinical trials. Over 700 people from academia, public institutions, and the pharmaceutical industry gathered to share their experiences, practices, insights, and perspectives on the more active use of data and information sciences in clinical trials.

Prof. Howard Lee spoke about AI-based patient recruitment in clinical trial in an invited session, entitled 'A Dimensionality Reduction Model to increase the Efficiency and Accuracy of Clinical Trial Feasibility Assessment using Electronic Medical Records(EMR)'. Prof. Lee emphasized the application of AI technology to clinical trial feasibility such as feature selection algorithms in machine learning to identify common sensitive eligibility features (cSEFs). 

Yoomin Jeon and Tae Chung presented a poster at the conference too. Yoomin's poster was about the actual application of what Prof. Lee introduced in his talk. Tae examined the extent of mapping of ICD-10 to MeSH to crosswalk and synchronize different terms collected from different data sources. (Analysis of agreement status between the diagnostic code of MeSH and ICD-10).

Meanwhile, Dr. Soohyun Kim led a tutorial session, where she taught several essential statistical methods for biomedical informatics research using R. 

For more details, you may want to contact Yoomin Jeon or Tae Chung.

Prof. Howard Lee has been recently awarded a government grant from the Small Grant Exploratory Research (SGER) Program through the National Research Foundation of Korea or NRF to develop a model for assessing clinical trials feasibility. The total research funding was $223,000 over a 3 year period (11/01/18 to 10/31/21), which is equivalent to 250 million Korean Won. After a year of an initial stage of research, funding may be continued for additional two more years based on satisfactory progress. The title of Prof. Lee's proposed research plan was "A Dimensionality Reduction Model to increase the efficiency and accuracy of clinical trial feasibility assessment using electronic medical records". This research aimed to develop a machine learning-based dimensionality reduction model to identify the common sensitive eligibility features (cSEFs) that could increase the efficiency of clinical trials feasibility in the presence of intended patient population characteristics. Feature Selection algorithms will be used to enhance the performance of this machine learning model. 

Prof. Howard Lee emphasized the importance of the holistic approach to ensure the safe use of biological agents, particularly in the field of rheumatology, at a policy forum sponsored by the Korean College of Rheumatology, held at the Seoul Foreign Correspondents' Club, Press Center, on November 14, 2018. Biological agents, since first introduced in the late 1990s, have changed the way that physicians managed patients with various connective tissue diseases, of which rheumatoid arthritis is a typical example. "Because biological agents are way different from small-molecule drugs in terms of their safety profiles, which most physicians are not familiar with", Prof. Lee said, "they have to be used carefully, preferably only by those who were trained how to correctly prescribe them and those who are experienced in detecting the adverse reactions, which often clinically manifested in atypical forms." "Reactivation of latent tuberculosis and increased occurrence of opportunistic infections are some examples", Prof. Lee added. Registries of patients using biological agents can be a useful tool to track down and detect adverse effects of biological agents, which are not easy to be screened out in clinical trials before marketing approval. In that sense, Prof. Lee requested the rheumatology society to be more proactive by initiating and maintaining a series of safety measures, hopefully under a full collaboration with and support by the regulatory agency. Most of the panelists at the forum agreed with Prof. Lee. 

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. 

Dr. Jeong-An Gim has been awarded a government grant from the National Research Foundation (NRF) of Korea on September 1, 2018 to study epigenetic/epigenomic changes after drug treatment. The grant will cover a year and the total research funding is $40,000 or ~40 million Korean Won. The title of Dr. Gim's research was "An Association Study Between the Pharmacoepigenomic Patterns of Drug-metabolizing Enzymes and the Pharmacokinetics of Tacrolimus", which aimed to identify several sensitive genetic regions associated with the pharmacokinetics of tacrolimus, an immunosuppressive agent frequently used in transplant patients. Blood samples for this proposed study have been already collected from two previous studies ( Choi et al., Kim et al., 2017 ), and the samples will be outsourced to Theragen Etex for the next generation sequencing (NGS) analysis. 

The proposed study is the first of its kind applying the state-of-the-art technologies to investigating the epigenetic/epigenomic effect on the exposure to tacrolimus in humans. Dr. Gim has been interested in finding an optimal epigenetic state to maximize the efficacy of a drug while minimizing potential adverse events, and tacrolimus will be his first bet. 

Prof. Lee congratulated Dr. Gim, saying "Converging the principles of clinical pharmacology, genomics, and eipgenetics/epigenomics, we will have a much better understanding how humans handle the administered drug." Prof. Lee added, "Dr. Gim's approach is innovative, and his research exemplifies how convergent approaches can be adopted to solve problems in drug development." 

The GSCST Blog interviewed Prof. Lee on a hot summer day early August, and the interview was featured in a GSCST Blog post. For more information, click here.

Ms. Jung Chun Gwon has joined CCADD on August 16th as an administrative assistant and accountant. In this capacity, Jung Chun will be assisting Profs. Howard Lee and Hyung-Jun Im of the TMT Laboratory, and will be also in charge of accounting in the research grants. Jung Chun studied economics at Sookmyung Women’s University, where she received a BA degree. 

Prior to joining CCADD, Jung Chun worked in the Korea Institute of Finance (KIF) as a secretary and research associate for eight years, where she was responsible for writing up research reports and proposals. Prof. Lee welcomed Jung Chun , saying "she will be a great addition to CCADD, helping us with various administrative tasks and activities, which have been often unattended". Please join us in welcoming Jung Chun to CCADD!

Two scientists from Samsung SDS, Mr. Jaeho Yang, Principal Engineer (Sr. Expert), IoT Lab, and Dr. Sunghoon Joo, PhD, Senior Engineer, Advance Research Lab, visited CCADD on August 24, 2018 to have a joint seminar. In this joint seminar, Prof. Howard Lee gave an overview of the research projects CCADD has performed in the area of applying the artificial intelligence (AI) technology to clinical drug development, entitled with 'AI-enriched Clinical Trials'. Prof. Lee emphasized how AI could streamline various research activities pertaining to clinical trials, one of which is patient enrollment. For example, it is important to know who did what and how before planning any clinical trial, which is the main theme of the grant that the Korea Clinical Trials Global Initiative or KCGI has recently awarded CCADD, named 'AI-based Clinical Trial Resource Integration System or ACTRiS',

Following Prof. Lee's presentation, Mr. Yang introduced CCADD to the core concepts of several AI technologies and their potentials in drug discovery. Recurrent Neural Network (RNN) and autoencoding (AE) were a few examples Mr. Yang put emphasis on during his presentation. After that, Dr. Joo expanded further on several research projects Samsung SDS has conducted to design new molecules for drug discover in silico using advanced AI technologies such as molecular graphs and AE. Collectively, Mr. Yang and Dr. Joo showed how AI could fasten the discovery of new drug candidates that are likely to maintain excellent bio-physico-chemical properties, which may save time, resources, and costs in the whole drug development program. 

CCADD and Samsung SDS agreed to continue looking for a cadre of collaboration and joint research opportunities that may benefit both organizations.   

Prof. Howard Lee demanded that generic approval in Korea be tightened by not allowing the so-called 'joint-bioequivalence' or 'consigned-bioequivalence' route at a Korea National Assembly Forum, co-sponsored by Rep. Yoon Il-Kyu of the ruling Democratic Party and the Korean Doctor's Weekly. The forum was held to go over various regulatory issues associated with the recent recall of valsartan-containing anti-hypertensive agents by the Ministry of Food and Drug Safety in a haphazard way, prompted by a similar regulatory action by the European Medicines Agency, which was caused by a concern that the active ingredient manufactured by a Chinese company contained NMDA, which could be carcinogenic in humans.

According to Prof. Lee, there were at least three regulatory practices that could have prompted the valsartan debacle in Korea: too low bar for generic entry into the market, lack of a consistent quality assurance system to ensure the quality of generics and their sources (active pharmaceutical ingredients), and too generous pricing for generics. "These unique regulatory systems for generics in Korea have favored the incompetent generic maker to enter the market rather unruly", Prof. Lee emphasized. Prof. Lee added, "Many pharmaceutical companies, most which were not unsure of their quality, got generics approved through the join- or consigned-bioequivalence testing, and this system needs to be abolished."

More detailed story about the Forum can be found in the following articles in Korean or English. 

Prof. Howard Lee has attended the 40th EMBC (Engineering in Medicine and Biology Conference), Honolulu, Hawaii, USA, on July 17-22. The theme of the meeting was “Learning from the Past, Looking to the Future”, inspired by the 40th anniversary of the world’s largest international biomedical engineering meeting.

In the Conference, Prof. Lee co-chaired a minisymposia with Prof. Kyung-Soo Park, Yonsei University, entitled 'Pharmacometrics Approaches & Novel Drug Delivery Systems in Pharmaceutical Engineering'. Prof. Lee also spoke about the ACTRiS project at the minisymposia, particularly with a strong emphasis on the importance of precision feasibility for clinical trials. The one-page abstract for Prof. Lee's presentation that he co-authored with one of his students, Yoomin Jeon, can be downloaded below. 

Prof. Howard Lee attended the 2018 Gordon Research Conference in Drug Metabolism, held at the Holderness School, NH, USA, July 8-13, 2018. The GRC in drug metabolism is presented every year for 48 years, which means the 50th Anniversary will come soon in two years. According to the GRC website, the conference focuses "on cutting edge research in drug ADME (absorption, distribution, metabolism, elimination), encompassing a wide range of research from the cellular level to the patient." Truly, the conference addressed a variety of topics in drug ADME, some of which, particularly for those which were presented on the first two days, were very basic. However, the remaining topics were of clinical or at least translational, so the mix was good. What was unique about the conference was its informal atmosphere. ~170 attendees had an ample opportunity of networking, not only in the conference room, but also in the dining room and bar after 9:30 PM. Additionally, there was a social activity such as hiking, soccer, soft ball and kayaking during 1:30-4:00 PM every day, which was fun! 

Prof. Lee met with old friends of his at the conference including Dr. Yuichi Sugiyama, the Sugiyama Laboratory, RIKEN, Japan and Prof. Sukyung Woo, University of Oklahoma Health Science Center, USA. The GRC in Drug Metabolism is a great refreshing opportunity for any involved in drug development, particularly for those who work in discovery, medicinal chemistry, preclinical DMPK, and lastly, but not the least, clinical pharmacology. 

"The recent recall of valsartan API made by Zhejiang Huahai (China) following detection of a potential carcinogen has revealed the weak and scientifically unsound basis of the generic approval system in Korea", Prof. Lee spoke in a telephone interview with KBS. Prof. Lee detailed about this issue in a newspaper column. The number of recalled valsartan generics in Korea was 115, which was way greater than that in the UK (only 8) and Japan (only 1). The reason behind this difference was that Korea has maintained a relatively low bar for the approval of generics. For example, any company can sell generics if they could obtain them from anyone who has a marketing authorization of the generic. In other words, the company is not necessarily responsible for the quality of the generic, nor they have to show that they could make a qualified generic, which meets all of the regulatory requirements including the proof of bioequivalence. 

As a result, there are numerous generics for a single original product. This, in turn, has introduced an exceptionally high competition among the companies, which has implicitly encouraged unethical business practices such as kick-back and unlawful rebates. The issue also has brought some quality issues to manufacturing of generics in Korea. For example, many companies have switched their API source after approval, mostly to a low-quality Chinese company, of which Zhejiang Huahai may be one. 

Therefore, to preempt the recurrence of this quality API source issue for generics in Korea, the approval system has to be heightened, Prof. Lee summarized.