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Objective: There have been many cases of spontaneous adverse drug reactions to fentanyl at a regional pharmacovigilance center in the hospital. To assess the factors causing the adverse drug reactions reported in patients receiving fentanyl patient-controlled analgesia (PCA) monotherapy or in combination with fentanyl transdermal therapeutic system (TTS) for acute post-operative pain management. Methods: We conducted a retrospective cohort study with all patients prescribed fentanyl PCA for pain management after orthopedic surgery at a single university hospital from June 2012 to May 2013. We analysed the factors causing adverse drug reactions reported by a spontaneous reporting system in patients receiving fentanyl PCA monotherapy and those receiving fentanyl TTS in combination with fentanyl PCA. Results: Based on the spontaneous adverse drug reaction reporting, the risk ratio for the incidence rate of adverse drug reaction in the fentanyl TTS combination therapy group was 3.04 (95 % CI: 2.4-4.00, P < 0.0001), which was approximately 3-fold higher than that reported for fentanyl PCA monotherapy. Only 60 % of the adverse drug reactions were reported. Conclusion: It is inappropriate to add fentanyl TTS to fentanyl PCA to manage post-operative acute pain. There is a need to improve adverse drug reaction reporting. We expect that regular analysis of adverse drug reactions reported at regional pharmacovigilance centre would aid in appropriate drug utilization by patients.

Background: We strived to evaluate the status of nivolumab use and associated factors on the clinical efficacy of the drug. Methods: The study was retrospectively conducted in patients who had been administered nivolumab at least once at the cancer center of Seoul National University Hospital from June 2015 to April 2017. Data were collected from electronic medical records. A medication-use evaluation was performed based on the American Society of Health-System Pharmacists mediation-use guidelines. Results: Sixty-six of the 74 patients (89.2%) showed indications approved for nivolumab use by the Korean Ministry of Food and Drug Safety (MFDS; n=55) or the US Food and Drug Administration (FDA; n=11). Approximately 73.0% of the patients were administered the approved dose of 3 mg/kg but 25.7% were administered an unapproved fixed dose of 100 mg. The overall response rate was 21.7%, and the response rate of non-small cell lung cancer patients, who accounted for the largest number of indications, was 18.8%. Adverse reactions were found in 90.1% of the patients and were mostly mild (86%). The expression of programmed death-ligand 1 (PD-L1) was analyzed as a factor affecting treatment response (p=0.028, odds ratio [OR]=11.331). Conclusion: PD-L1 expression was found to affect treatment response. However, caution is required while using an unapproved dosage and in the absence of monitoring for effectiveness and safety. Therefore, an effective protocol or instruction manual for the proper use of nivolumab should be considered.

Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that can affect many organs of the body but usually affects the lungs. The prevalence of TB in Korea is considerably higher than that in other countries with similar economic levels, and is much higher in elderly people. Pharmacotherapy is important in the treatment of TB and requires relatively high compliance for a prolonged duration. Methods: We analyzed sample data of elderly patients obtained from the Health Insurance Review and Assessment Service. We used logistic regression analysis and frequency analysis to identify factors that could affect prevalence of TB in elderly patients, compliance with prescribed medication regimes in these patients, and use of medical institutions. Korean Standard Classification of Diseases, version 7 (KCD-7) was used to diagnose pulmonary TB, and medications were analyzed using Korean standardized drug classification codes. Results: 1,276,331 patients were analyzed in the sample of the elderly population, and 16,658 TB patients were included in the study. The mean age of the TB patients was 76.19 years (SD 6.899). A total of 699 patients were prescribed isoniazid, rifampicin, ethambutol, or pyrazinamide at least once. Of these, 352 (50.4%) were prescribed all four medications and 101 (14.4%) were prescribed only isoniazid, rifampicin, and ethambutol. The mean duration of prescription was 28.75 days (SD 36.13). Conclusion: In the elderly population, old age and poor socioeconomic conditions correlated with TB prevalence. Most patients did not meet the criteria for effective pharmacotherapy of TB.

ABSTRACT Objective: The purpose of the study was to investigate the time from the injection of muscle relaxants to the first spontaneous respiration between sugammadex and conventional reversal for patients undergoing laparoscopic cholecystectomy. Methods: This study was retrospectively conducted on patients who were diagnosed with gallbladder stone (N802) between January 2014 and April 2017. The data were collected from the electronic medical records of a total of 186 patients (84 patients in the neostigmine group and 102 patients in the sugammadex group). Results: The time required for the first spontaneous respiration in the sugammadex group was shorter than that in the neostigmine group (3.6 min vs 4.9 min; p<0.05). After the injection of intermediate muscle relaxants, the comparison of heart rate and mean arterial pressure in the sugammadex and neostigmine groups revealed that the heart rate in the neostigmine group was higher than in the sugammadex group after 5 min (p<0.05). The mean arterial pressure in the neostigmine group was higher than in the sugammadex group after 10 min (p<0.05). A significant adverse effect of tachycardia was observed in the neostigmine group (p<0.05), but the frequency of rescue antiemetic in the sugammadex group was significantly higher than in the neostigmine group (p<0.05). Conclusion: In this study, the unwanted effect of neostigmine group was tachycardia; therefore, in the case of patients with hemodynamic instability, sugammadex is recommended. At 12 hours after the injection of sugammadex to patients, more antiemetics were required than in the neostigmine group; therefore, more research should be conducted on postoperative nausea and vomiting.

Objective: This study analyzed the national claims data of veterans to generate scientific evidence of the trends and appropriateness of their drug utilization in an outpatient setting. Methods: The claims data were provided by the Health Insurance Review & Assessment (HIRA). Through sampling and matching data, we selected two comparable groups; Veterans vs. National Health Insurance (NHI) patients and Veterans vs. Medical Aid (MAID) patients. Drug use and costs were compared between groups by using multivariate gamma regression models to account for the skewed distribution, and therapeutic duplication was analyzed by using multivariate logistic regression models. Results: In equivalent conditions, veteran patients made fewer visits to medical institutions (0.88 vs. 1), had 1.86 times more drug use, and paid 1.4 times more drug costs than NHI patients (p<0.05); similarly, veteran patients made fewer visits to medical institutions (0.96 vs. 1), had 1.11 times more drug use, and paid 0.95 times less drug costs than MAID patients (p<0.05). The risk of therapeutic duplication was 1.7 times higher (OR=1.657) in veteran patients than in NHI patients and 1.3 times higher (OR=1.311) than in MAID patients (p<0.0001). Conclusion: Similar patterns of drug use were found in veteran patients and MAID patients. There were greater concerns about the drug use behavior in veteran patients, with longer prescribing days and a higher rate of therapeutic duplication, than in MAID patients. Efforts should be made to measure if any inefficiency exists in veterans’ drug use behavior.

Background: Prostatitis, one of the most common diseases of the prostate, is a complex disease with various clinical features. This study aims to analyze the utilization and prescribing patterns of antibiotics in Korean patients with prostatitis between 2008 and 2015. Methods: We used the National Health Insurance Database complied from the Health Insurance Review and Assessment Service (HIRA). The outcomes included the number of claims, number of patients, medical cost, and length of stay for each year. In addition, the prescribing patterns of antibiotics, including fluoroquinolone, and low-dose use of ciprofloxacin and levofloxacin were investigated. Results: The total number of patients and medical cost increased by 9.5% and 51.7% from 2008 to 2015, respectively. Most prostatitis patients were classified as chronic prostatitis patients. The prescribing proportion of antibiotics for chronic prostatitis outpatients decreased from 71.0% to 66.9% from 2008 to 2015, and fluoroquinolone accounted for more than half of the total antibiotics. Over 80% of prescription of levofloxacin and ciprofloxacin was identified to be for low-dose use. Conclusion: Most of the patients with prostatitis experienced pain relief and condition improvement after antibiotic treatment; however, chronic prostatitis and chronic pelvic pain syndrome recur easily. Therefore, active disease management and further studies are needed to enhance our understanding of effective treatment for prostatitis.

Objective: This study examined the Risk Sharing Agreement (RSA) on pharmaceutical pricing system in Korean national health insurance. Through RSA, the insurer was able to maintain the principles in the price listing process while managing the budget effectively and improving patient access to new drugs. Despite these positive effects, there are still issues raised by some stakeholders, such as lack of transparency in the listing process and doubts about its effectiveness. Therefore, we investigated the impacts of RSA on national health insurance financing and patient access to analyze the effects of RSA. Methods: The impact of RSA was investigated by analyzing the health insurance claims data for 2014∼2016. The degree of improvement in patient access was determined by the decreased amount of patients’ payment. Results: Results showed that the financial impact of RSA was not significant and patients’ access to the new drug greatly improved. Conclusion: These results show that RSA is a good system for improving patient access to new drugs without additional expense on insurance.

Background: In South Korea, 22.3% of women ≥50 years of age and 37% of women ≥70 years of age visit the doctor to obtain treatment for osteoporosis. According to the analysis of the National Health Insurance Services claim data between 2008 and 2012, the number and incidence of hip and vertebral fractures increased during the same period. Denosumab, a newly marketed medicine in Korea, is the first RANK inhibitor. Methods: A cost-utility analysis was conducted from a societal perspective to prove the superiority of denosumab to alendronate. A Markov cohort model was used to investigate the cost-effectiveness of denosumab. A 6-month cycle length was used in the model, and all patients were individually followed up through the model, from their age at treatment initiation to their time of death or until 100 years of age. The model consisted of eight health states: well; hip fracture; vertebral fracture; wrist fracture; other osteoporotic fracture; post-hip fracture; post-vertebral fracture; and dead. All patients began in the well-health state. In this model, 5% discounted rate, two-year maximum offset time, and persistence were adopted. Results: The total lifetime costs for alendronate and denosumab were USD 5,587 and USD 6,534, respectively. The incremental costeffectiveness ratio (ICER) for denosumab versus alendronate was USD 20,600/QALY. Given the ICER threshold in Korea, the results indicated that denosumab was remarkably superior to alendronate. Conclusion: Denosumab is a cost-effective alternative to the oral anti-osteoporotic treatment, alendronate, in South Korea.

Background: Presently, a multidisciplinary team of doctors, pharmacists, nurses, and dietitians provides patient education to impart information on chemotherapy. However, studies on multidisciplinary education satisfaction are inadequate. In this study, we aimed to contribute to the improvement of quality of multidisciplinary education counseling for patients with cancer by developing a satisfaction questionnaire and analyzing the satisfaction survey. Methods: A questionnaire was developed by an expert group, and the responses were recorded using the 5-point Likert scale. After conducting a pre-test, factor analysis was performed to evaluate validity. The reliability of the questionnaire was measured by Cronbach’s alpha coefficient. A satisfaction survey was conducted by self-administration method. Results: Based on the results of factor analysis, factors can be divided into two parts: “overall education” and “each team member’s education” (total 14 questions). The construct validity and reliability of the questionnaire are sufficiently high. Fifty-one patients took the survey between January 2, 2018 and January 20, 2018. Twenty-six (51%) patients responded that they were “very satisfied” and 22 (43.1%) patients responded that they were “satisfied”. Conclusion: By developing a questionnaire on multidisciplinary education counseling for patients with cancer, it is possible to perform evaluation and research of cancer patient education. This study will contribute to the management and improvement of quality of multidisciplinary education.

Objective: Multi-regional clinical trials have been widely used for accelerating global drug development by multinational pharmaceutical companies. In this study, we aimed to review and analyze the international trends in regulations and guidelines on multi-regional clinical trials by regulatory authorities and international organizations, such as International Conference on Harmonisation, for referring to policies, including development of domestic guidelines for multi-regional clinical trials. Methods: The policies, regulations, and guidelines published by the US Food and Drug Administration, European Medicines Agency, Pharmaceuticals and Medical Devices Agency (Japan), and China Food and Drug Administration were searched, and the International Conference on Harmonisation E17 draft guideline was reviewed. Results: The regulatory authorities in developed countries have developed and implemented regulations and guidelines on multi-regional clinical trials to promote simultaneous global drug development and evaluate the regional differences in drug safety and efficacy. International Conference on Harmonisation developed the draft guideline for planning/designing of multi-regional clinical trials in 2016, which recommends the general principles for strategy-related issues and design of multi-regional clinical trials, and for protocol-related issues, such as consideration of regional variability, subject selection, dose selection, endpoints, comparators, overall sample size, allocation to regions, collecting information on efficacy and safety, and statistical analysis. Conclusion: It is important to understand the international regulatory requirements for designing and planning of multi-regional clinical trials for global drug development. Moreover, it is necessary to prepare multi-regional clinical trial guidelines in accordance with the Korean regulation for clinical trials and drug administration.

Levosulpiride is one of the most frequently prescribed medicines in Korea. An adverse drug reaction (ADR) after taking levosulpiride was reported at a community pharmacy in Korea. A 31-year-old woman reported the symptoms of lactation and amenorrhea after taking levosulpiride; an evaluation of whether these symptoms were caused by the medication was therefore necessary. Several tools can be used to determine if the ADR resulted from the administered drug or other factors, including the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) criteria, the Naranjo scale, and the Korean causality assessment algorithm (Ver. 2). The causality was evaluated as “possible” by the WHO-UMC and Naranjo scales, but as “probable” by the Korean causality assessment algorithm (Ver. 2). In conclusion, the information provided did not indicate definite causality and there were slight differences in the results obtained from each assessment method.