The registration of new drug is more difficult every year because health authority requests more data on efficacy and safety, especially in long-term clinical trials. In Korea, health authority usually requests bridging data in Korean subjects in order to evaluate the possibility of extrapolation of foreign data to Korean population. But multinational developmental clinical trials from phase 1 to 3 in Korea are ongoing increasingly and it is the time to evaluate the clinical data in the viewpoint of global drug development. Sometimes phase 3 trial for Koreans only may be the waste of resources and the barrier to delay the access for Korean patients even though the drug is available in other countries some years earlier. In scientific point of view, other methods such as Pharmacokinetics / Pharmacodynamics simulation and modeling may be the one of the options to evaluate the ethnic sensitivity. In this article, I explain the issues in the generation of bridging data using additional Koreans only phase 3 trial and the possible alternative for the future.

The Declaration of Helsinki was originally adopted by the World Medical Association (WMA) in 1964, and has undergone six revisions. The most recent revision was made in October 2008 in Seoul, Korea. The Declaration of Helsinki is the most widely known international guideline to provide the ethical principles for medical research involving human subjects. As the number of clinical researches has been increasing markedly in Korea, there are growing expectations and concerns about the research ethics related to the protection of human subjects. Physicians conducting the clinical research are supposed to know and understand the content of the Declaration, and they should follow the guideline in their researches. The current structure of the Declaration has three parts: Introduction; Basic Principles for All Medical Research; and Additional Principles for Medical Research Combined With Clinical are. It includes essential elements of the ethical principles for clinical research, such as informed consent, research ethics committee, and risk-benefit assessment. Although there have been continuing controversial issues in the Declaration of Helsinki, it will remain to be the cornerstone of research ethics.

Introduction: Currently, the adverse events are being inspected, aiming to prove the safety from phase 1 up to phase 4 of clinical study to Post Marketing Surveillance (PMS). Along with the movement of the changing international society, an auto coding system that is developed based on the existing MedDRA was devised to provide medically consistent and accurate as well as commonly applicable terminologies in the field of medicine while aiming to share the clinical safety of the medical supplies oriented by the ICH countries. Material and Methods: The auto coding system developed in this study basically connected the 67,159 LLT terminologies from MedDRA 12.0 and 5,583 terminologies from WHO-ART 2006, while improving the coding efficiency by utilizing the existing coding data. As for the comparison between the Copy & Paste Method (hereinafter called as 'CPM') and AE Mapper (hereinafter called as 'AEM'), which was an auto coding system, the assessment was made in terms of efficiency, accuracy, and consistency. In addition, the difference depending on the level of medical background among the coders' skill was measured when comparing CPM and AEM. Result: In case of comparing CPM and AEM, the time consumed for CPM was 4.5 times greater than AEM. When comparing the accuracy, the file of the experiment 1 did not display a significant difference resulting CPM 86.7% and AEM 94.9% of the total average; however, the file of experiment 2 showed a significant difference as CPM was 62.0% and AEM was 92.4% in terms of the total average. When comparing the consistency, the file of the experiment 1 did not display a significant difference resulting CPM 89.0% and AEM 99.3% of the total average; however, the file of experiment 2 showed a significant difference as CPM was 79.6% and AEM was 98.9% in terms of the total average. Conclusion: Based on the result derived by comparing CPM that copied and pasted AE and AEM (AE apper) that was an auto coding system for coding AE, it was known that the use of the auto coding system was superior in terms of efficiency, accuracy, and consistency. Furthermore, when using the auto coding system, there was no significant difference depending on the users’ medical background and past experience in terms of accuracy and agreement compared to the CPM. Therefore, it is suggested to seek a method to improve the mapping of the auto coding system and conduct a further study that applies such system.

Background: Theobromine, an alkaloid naturally present in green tea, coffee, and cocoa, is known to possess properties of cardiac stimulation and antitussive effects. The aim of this study was to compare the pharmacokinetic (PK) characteristics of two different formulations (suspension and capsule) of theobromine in healthy male volunteers. Methods: A randomized, open-label, multiple-dosing, two-treatment, two-period, two-sequence, crossover study was conducted in Clinical Trials Center, Seoul National University Hospital with 12 healthy male volunteers. Subjects orally received either theobromine suspension 300 mg or capsule 300 mg twice daily for 4 days and crossover phases were separated by a 7-day washout period. Plasma samples were collected before dosing and up to 12 hr after the last administration. Plasma theobromine concentrations were determined by liquid chromatography-tandem mass spectrometry. PK parameters were estimated by a non-compartmental analysis. Results: Median time to peak concentration of theobromine suspension and capsule groups ere 0.33 and 2.50 hr, respectively. The mean [SD] values for peak concentaration at steady state ($C_{max,ss}$) and area under the plasma concentration-time curve during dosing interval at steady state ($AUC_{\tau,ss}$) for suspension (13.90 [3.66] mg/L and 113.31 [31.95] $hr^*mg/L$) did not differ statistically from those of capsule (13.26[3.76] mg/L and 122.96[41.47] $hr^*mg/L$). The geometric mean ratios (90% confidence intervals) for suspension to capsule were 1.05 (0.95-1.16) for $C_{max,ss}$ and 0.92 (0.85-1.00) for $AUC_{\tau,ss}$. Conclusion: These findings suggest that theobromine suspension 300 mg is similar to the corresponding dose of capsule 300 mg in terms of pharmacokinetic properties except the time to peak concentration at steady state.