CCADD is breaking the ground for biomedical natural language processing or NLP!

On January 22^nd, 2021, CCADD was nominated by the Ministry of Food and Drug Safety to develop an NLP model that extracts core clinical information from unstructured data in the Korea Adverse Event Reporting System (KAERS). The total research fund amounts to two hundred million Korean won or a hundred and eighty thousand U.S. dollars. The project will be performed in collaboration with the Machine Intelligence lab in the Department of Electrical and Computer Engineering, Seoul National University (Prof. Gyo-Min Jung). 

For starters, CCADD will build a manually annotated dataset, which is indispensable to train and refine any machine learning algorithm including NLP. Next, CCADD plans to build the KAERS-BERT model, an NLP model specifically tuned to handle adverse drug events. The KAERS-BERT model will be pre-trained on KAERS text data, which then will be deployed to extract medical information from free texts, such as hand-written records of adverse events. Once complete, the KAERS-BERT model is expected to address many of the language ambiguities caused by the mixed use of English and Korean in medical domains already peppered with technical and medical jargons. The KAERS-BERT model will significantly improve the performance and the outcome of NLP tasks when extracting information from clinical notes written in English and Korean. 

Prof. Howard Lee, the PI of the grant, congratulated the team, saying "The grant awarding is timely and important since it will help CCADD enter a new area of biomedical NLP." At the conclusion of this project, CCADD will once again have secured its place as the leading lab in the field of convergence science between medicine, drug development, and machine learning including NLP. "This certainly provides CCADD with a momentum to transform into a frontrunner in the field", Prof. Lee added.

Prof. Howard Lee has officially expressed strong disapproval of the reimbursement for 'cheobyak' or the mixture of herbal (or natural products-derived) drugs. In a roundtable provoked by the impending reimbursement decision of cheobyak by the Korea National Health Insurance Service against the objections by medical and scientific societies altogether, Prof. Lee raised intense disagreement with the government policy to support reimbursement of cheobyak. Prof. Lee argued that cheobyak has never been shown to be efficacious and safe through scientific assessments by the regulatory agency such as the Ministry of Food and Drug Safety in Korea, not to mention its uncertain quality as a medicine. He continued, discussing "The cost-effectiveness of any cheobyak has never been validly studied and confirmed, which is the minimal requirement for any drug approved and listed for health insurance reimbursement in Korea." 

A summary of Prof. Lee's presentation at the roundtable can be found in many newspaper articles, one example of which is here. Additionally, his full presentation has been uploaded to YouTube as seen below:        

Six undergraduate students (Sung Jong Kim, Hwe Won Kim, Jinyeong Yang, Song Yeon Oh, Chae Jeong Lee, and Yura Hwang) joined CCADD for the 2020 Winter Smart Internship, and they will spend the next 8 weeks in exploring the research environment at CCADD while having opportunities to participate in the ongoing research projects.

Sung Jong Kim is a fourth-year undergraduate student at Hankuk University of Foreign Studies, double majoring in Molecular Biotechnology and English-Korean Interpretation and Translation Studies. Studying biology and biotechnologies, Sung Jong has developed a broad interest in pharmacology and computer science. He is looking forward to learning NONMEM, an analysis program for pharmacokinetic pharmacodynamic (PKPD) modeling, during his internship program.

Song Yeon Oh is also a senior student at HanKuk University of Foreign Studies, and has studied Environmental Science. Song Yeon's research interests include applying artificial intelligence (AI) technologies into the pharmaceutical area to make drug development processes more efficient. During the internship program, she wants to learn methods to analyze medical data using computer language, such as Python and R, by participating in the CCADD's current projects.

Chae Jeong Lee is a second-year student at HanKuk University of Foreign Studies, majoring in Biomedical Engineering and Computer and Electronic Systems Engineering. Being familiar with C and Python, Chae Jeong wants to participate in CCADD's current AI projects such as those awarded by National Institute of Food Drug Safety Evaluation (NIFDS) and South Korean Ministry of Trade, Industry, and Energy (MOTIE). Through this winter internship program, she is looking forward to learning R to improve her coding skills.

Hwe Won Kim is a fourth-year undergraduate student at Konkuk University. She studies Converged Material Engineering and Environmental Engineering. Prior to the internship program at CCADD, Hwe Won worked as an intern researcher in the Department of Stem cell and Regenerative Biotechnology laboratory and has become interested in pharmacology and AI technologies. Through the internship program, she is looking forward to learning the basics of clinical pharmacology and AI algorithms applicable to pharmaceutical area.

Jinyeong Yang is a second-year student at College of Agriculture and Life Sciences, Seoul National University. Jinyeong was involved in research project project to develop a liquid bandage for patients with atopy to prevent potential secondary infections. Through her past experience, Jinyeong has become more interested in PK, PD, and development process of a drug. She is looking forward to learning the pharmacology and drug development process, as well as experiencing the research environment in graduate school. 

Yura Hwang is a senior student at Pusan University with a major in Molecular Biology and a minor in Chemistry. Previously, Yura worked in PRG S&T, a pharmaceutical start-up, where she has developed an interest in theoretical and computational methods to describe variability in PK. She is looking forward to learning NONMEM during her internship program.

This 2020 winter internship program will provide participants with opportunities to learn clinical pharmacology, machine learning algorithms, and computer languages for data analysis as shown below. CCADD wholeheartedly welcomes the 6 intern students, and hopes them to enjoy, learn, and experience as much as they want and can during the rest of their internship programs.

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.

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.

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. 

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. 

Three CCADD members (Dr. Jeong An Gim, Yoomin Jeon, and Tae Kyu Chung) attended the Pharma AI & IoT 2018 conference, held in London, UK, from July 11 through 12, 2018. Many invited from pharmaceutical companies, software firms, and universities spoke at the conference. The conference provided a comprehensive outlook on the key issues about artificial intelligence (AI), which has been actively adopted at the pharma and healthcare industry. AI-augmented human decision-making was the central theme of the conference. Dr. Margaret McDonald from Pfizer told the audience machine learning or AI would increase efficiencies in regulatory decision-making. She added, "Unsupervised AI may integrate enormous amounts of data and those real world data support regulatory decision-making about drug safety." Likewise, many attendants emphasized the importance of AI in their field of specialization. During the conference, attendants discussed and shared best practices in furthering AI technology development specific to the pharma and healthcare industry through inspiring presentations and network opportunities.

After the conference, the CCADD attendants visited several landmarks in London such as the Greenwich Observatory, Tate Modern museum, and London Eye. Amazing weather and the scenic view of London was a big plus. Visiting London was a great refreshing and learning opportunity.

Cross J, Lee H, Westelinck A, Nelson J, Grudzinskas C, Peck C. Postmarketing Drug Dosage Changes of 499 FDA-Approved New Molecular Entities, 1980-1999, Pharmacoepidemiology and Drug Safety, 2002;11:439-446.