1. RFP : 백신 이상반응 연구 및 안정성, 유효성 품질평가 기술개발

2. 해당분과 : 3-3 과제

3. 과제명 : 안전한 예방접종을 위한 이상반응 실마리정보 검색과 인과성평가 연구 네트워크 (K-CISA 프로젝트)

4. 연구책임자 : 신주영(성균관대학교)

[Abstract]

Background Adverse events (AEs) not listed on drug labels have recently been reported in young girls vaccinated against HPV, but signal detection related to the human papillomavirus (HPV) vaccine has never been conducted in South Korea using the Korea Adverse Event Reporting System database of Korea Institute of Drug Safety & Risk Management at Ministry of Food and Drug Safety. Objective To analyze signals associated with HPV vaccines using the Korean spontaneous AEs reporting system and data-mining methods and compare the results to current vaccine label information in South Korea and the United States of America, United Kingdom, European Union, and Japan to detect signals not currently listed on the labels. Setting We evaluated the Korea Institute of Drug Safety & Risk Management database from January 2005 to December 2016. After pre-screening the data, the adjusted total numbers of HPV-related AE reports and AEs were 2566 and 4748 and those of all other vaccine-related AE reports and AEs were 21,878 and 120,688, respectively. Methods Three data mining algorithms (proportional reporting ratio, reporting odds ratio and information component) were used to assess AEs. A signal was defined when the criteria for all three indicators were satisfied. The detected signals were compared to the label information of HPV vaccines from South Korea, the United States of America, United Kingdom, European Union, and Japan. Main outcome measure Signals of AE after HPV vaccination, which met all three data mining indices. Results In this study, we found a total 97 signals of AE after HPV vaccination. Of these, 78 AEs were already present on the HPV vaccine labels of South Korea and the following 19 AEs were not listed: neuralgia, tremor, neuritis, depersonalization, axillary pain, personality disorder, increased salivation, peptic ulcer, circulatory failure, hypotension, peripheral ischemia, cerebral hemorrhage, micturition disorder, facial edema, ovarian cyst, weight increase, pain anxiety, oral edema, and back pain. Moreover, AE information on the current HPV vaccine labels of South Korea, the United States of America, United Kingdom, European Union, and Japan was inconsistent. When comparing the 19 AE signals that were not listed on the drug label in South Korea with the labels from the other countries, neuritis, axillary pain, cerebral hemorrhage, facial edema, pain anxiety, and back pain appreared on the U.S. Food and Drug Administration HPV vaccine labels but not on the United Kingdom labels, and hypotension was listed only on labels in the European Union and Japan. Conclusions South Korea should develop a system for proactively updating HPV labels. These results also suggest potential research directions such as vaccination label expansion, pharmacovigilance studies, and identification of causality in AEs associated with HPV vaccination.