The informed consent process (ICP) is still not enacted adequately despite its importance in clinical research. The researches on ICP have been mostly focused on the process to get a signature on the informed consent form and have not investigated ICP in a broad perspective. This article presented a novel classification of ICP closely related with the whole process of clinical research. ICP swere classified into 3 major stages, i.e. ICPs before, during and after the execution of clinical research. The first ICP before the execution of clinical research is composed of 3 detailed stages; 1) planning stage of clinical research, 2) preparatory stage of ICP, and 3) review stage of ICP. The second ICP, which is done during the execution of clinical research and a well-known ICP from the current narrow perspective, has 4 detailed stages; 1) notifying stage of clinical research, 2) providing stage of clinical research information, 3) deciding stage of clinical research participation, and 4) ICP stage during the execution of clinical research. The last ICP done after the execution of clinical research consists of 2 stages; 1) closing stage of clinical research, and 2) stage of sharing research results and final review. The activities, problems and ways to improve ICP in each detailed stage were further discussed.

Background: Irsogladin maleate, increasing gastric mucosal blood flow and cAMP in mucosal epithelial cells, is being marketed for the treatment of gastric ulcer and gastritis. The object of this study was to evaluate the pharmacokinetic characteristics and safety profiles of irsogladin maleate in Koreans. Methods: An open-label, dose-escalation, parallel group study was conducted in 28 healthy male Korean volunteers. Irsogladin maleate was administered as a single dose of 4 mg (n=16), 8 mg (n=6) or 16 mg (n=6). Serial blood samples for pharmacokinetic analysis were taken over 504 h. Plasma concentration of irsogladin was measured by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters were determined using noncompartmental methods. Laboratory tests, ECGs, vital signs and physical examinations were performed for clinical safety evaluation. Results: Maximum observed irsogladin plasma concentration ($C_{max}$) (mean $\pm$ SD) of 4 mg, 8 mg and 16 mg dosage group were $82.9\;{\pm}\;12.5{\mu}\;g/L$, $161.4\;{\pm}\;25.9\;{\mu}g/L$ and $292.6\;{\pm}\;51.2\;{\mu}g/L$, respectively. Area under the plasma concentration versus time curve from dosing to the last quantifiable concentration ($AUC_{last}$) of three dosage groups were $12694.4\;{\pm}2906.2\;{\mu}g\;{\ast}h/L$, $24970.0\;{\pm}\;5253.8\;{\mu}g\;{\ask}h/L$,$47125.3\;{\pm}\;8676.7\;{\mu}g\;{\ast}h/L$, respectively. Apparent clearance ($0.30\;{\pm}\;0.07L/H$, $0.31\;{\pm}\;0.10\;L/H$, $0.31\;{\pm}\;0.06\;L/H$, respectively) was unaffected by dosage. The 95% CI of slope of Dose-$C_max$ and Dose-$AUC_{last}$ linear regression were 15.4-19.6 and 2485.2-3262.0. All adverse events reported were mild and no clinically significant abnormalities of safety evaluation were observed. Conclusions: The pharmacokinetic characteristics of Irsogladin maleate after single dose dministration was explored in healthy Korean volunteers. Irsogladin maleate displayed linear plasma pharmacokinetics over the dose range 4-16 mg. Irsogladin maleate was well tolerated after single dose administration in Koreans.

As there has been substantial increase in the number of multicenter clinical trials in Korea, sponsors and investigators are concerned about the duplication of effort and delay by multiple IRB reviews. To enhance the efficiency of IRB in multicenter studies, the introduction of joint IRB or central IRB has been discussed. Although the Korean Good Clinical Practice(KGCP) was revised to accept centralized IRB review process in 2007, joint IRB has not been used in most institutions. Two models of joint IRB, single non-profit IRB and multiple lead IRBs, are applicable considering the current situations of IRB in Korea. The concept and operation of the two models have been described in this article. The governmental initiative and operational guidelines are the prerequisites for the successful implementation of the nationwide joint IRB in Korea.

Background: Clopidogrel is a prodrug converted to active metabolite mainly by cytochrome P450 (CYP) enzyme, and provides clinical benefitwith wide interindividual variability. We investigated to evaluate the effect of CYP2C19 genetic polymorphism and coadministration with ketoconazole on the platelet aggregation response to clopidogrel. Methods: An open-label, two-treatment, two-period, one-way crossover study with a drug-free period of five days or more was conducted in healthy male volunteers. First, a single dose of 300 mg clopidogrel was administered to carriers of at least one CYP2C19 loss-of-function allele (n=10) and non-carriers (n = 12). After a drug-free period, a single dose of 300 mg clopidogrel was administered with400 mg ketoconazole daily for 3 days. Platelet aggregation was measured at baseline, 4 h, 6 h, and 24 h using Chronolog Lumi-Aggregometer. Results: Maximal platelet aggregation at baseline was not different across CYP2C19 genotype. CYP2C19 loss-of-function allele carriers had significantlyless reduction in platelet aggregation at 24 h than non-carriers whether clopidogrel was administered alone (P=0.018) or with ketoconazole (P=0.011). In addition, relative inhibition of platelet aggregation at 24 h was lower after coadministration with ketoconazole than clopidogrel alone (P<0.001). Conclusions: Platelet aggregation response to clopidogrel was affected by CYP2C19 genetic polymorphism and coadministration with ketoconazole.

Background: Due to the strong relationship between successful clinical trial result and subject's high compliance to protocol, this research aimed to provide the basic information of the key factors affecting subject's compliances to improve the quality of the clinical trial. Method: The cross sectional study was retrospectively investigated with the result of the phase III clinical trial which had been conducted with co-participation of investigators belonged to two different medical specialties involving 15 university affiliated hospitals. The factors were classified into subject factor, institution factor, principal investigator factor, study staff factor and clinical research associate (CRA) factor. The collected data was tested at significance level of 5% using SAS program and analyzed by chi-square test, multiple logistic regression analysis and stepwise multiple regression analysis. Result: Among subject's compliances, the factors affecting the visit completion and medication compliance were come out differently. In terms of the visit completion, as a result of stepwise multiple regression analysis, the rate of visit completion was 4.9 times higher in the group of subjects taking corticosteroids than others, which is significant. In addition, the rate of visit completion was 10 times and 6.5 times respectively higher with principal investigators and clinical research coordinators belonging to the department in charge of the subject enrollment with subject's underlying disease treatment than the department in charge of the tests during the clinical trial, which is significant. Particularly, in terms of medication compliance 80% of investigational product medication compliance was shown in the group of no CRA change which is 4.0007 times significantly higher than others. Conclusion: Among subject's compliances, the significantly high influential factor for the visit completion was the subjects taking corticosteroids which were one of the risk factor for peptic ulcer and the specialty factor in charge of the continuous treatment for subjects and its principal investigator. Also, the factor which had significantly highly affected subject's medication compliance was CRA factor. Since subject's compliances were limited with the visit completion and medication compliance in this study, further investigations about subject's compliance are required. Also, it will be necessary to investigate CRA's indirect influence to subject's medication compliance in detail in the future.

Background: The questionnaires were answered by the patients and their family members who visited the hospitals, the staffs in the hospitals, and the personnels who are involved with clinical trials such as the physicians, pharmacists and nurses for the purpose of surveying the cognition on clinical trial and informed consent. This study was performed in order to provide with the basic information and/or data for supporting to motivate the clinical trials by analyzing the factors affecting the difference of the cognition on each item. Method: The number of whom responded to the questionnaires was 310 in total, which was composed with 137 patients and their family members, 109 staffs in the hospitals, and 64 personnels involved with clinical trials. Result: Most of them were well acquainted with clinical trial, and knew that it is the processes to identify the safety and efficacy with the patients and it has been done in the big hospitals like university hospitals. As the results of surveying the cognition on the processes of clinical trials, most of them were known well but something was not recognized like the patients’ right to see their medical history records. While the expectation which can be obtained by participating in clinical trials was not so big, the biggest one was to get more advantageous benefits (efficacy) from clinical trial. With regard to the cognition on the informed consent, it was well understood its basic concept and procedures. The responders who participated in clinical trials before answered they regard that to conduct the clinical trial is more ethic and the mandatory process to develop the new drugs rather than what those that did not participated in the clinical trials, by 2.0 and 2.7 times, respectively. From the points of general relations considering the participation in clinical trials, the persons with diseases show more experience to participate in it, by 5.8 times, rather than those without diseases, and the persons with medication have 4.8 times more experience in participate in clinical trials than those who do not take the drugs. In addition, the persons who have participated in clinical trials showed more willingness to participate in clinical trials than those who have not participated in it. Conclusion: From the survey results by the questionnaire, considering the current circumstances that the numbers of clinical trials has been rapidly increasing, it was found and is recommended that the persons participating in clinical trials should continuously give the patients and their family members more correct and useful knowledge and information on clinical trials and at the same time that the patients should make their efforts to acquire the adequate information and their duties on clinical trials and make decision of their participation in clinical trials by themselves.

류마티스관절염의 치료전략으로는 항류마티스약제를 이용한 단계적 치료가 일반적이다. 최근에 개발되어 류마티스관절염의 중요한 치료제로 자리매김한 종양괴사인자억제제는 관절염의 증상 감소 외에도 질환의 진행을 억제하는데 매우 효과적인 것으로 알려져 있다. 이러한 우수한 효과로 인해 종양괴사인자억제제의 조기사용의 필요성이 강조되고 있으나 높은 의약품비는 이를 초기치료약물로 사용하는데 있어 제한점으로 지적되고 있다. 목적: 대표적인 종양괴사인자억제제인 etanercept (ETN)을 포함한 한국인 류마티스관절염 환자의 치료전략에 있어서, ETN을 초기약물치료로서 사용하는 치료전략을 현재 일반적으로 시행되고 있는 타약제에 저항성을 보일 경우에 ETN을 사용하는 후기사용전략에 대한 비용-효과를 판단하고자 하였다. 방법: 한국인 류마티스관절염 환자에서 MTX단독요법 후에 MTX와 leflunomide (LFN)병합요법에 저항성을 보일 경우 ETN와methotrexate (MTX)병합요법을 사용하는 후기사용전략에 대하여 초기부터 ETM와 MTX를 사용하는 조기사용전략의 비용효과분석을 시행하였다. 단기간의 임상시험 결과들에 대해 Markov cohort simulation을 시행하였으며, 6개월간의 Health Assessment Questionnaire disability score의 경향을 1,000명에 대해 5년간의 변화를 시뮬레이션하였으며, 이를 성과지표로서 질보정수명 (quality-adjusted life year: QALY)으로 환산하였다. 의약품 및 검사비와 같은 직접의료비용은 한국의 국민건강보험수가를 기준으로 하여 계산하였다. 결과: 5년간의 시뮬레이션에서 ETN의 조기사용전략에 있어서 후기사용전략에 대한 점증적 비용효과비(Incremental cost-effectiveness ratio: ICER)는 1QALY당 78,101(천원)로 계산되었다. 이를 10년, 15년, 30년으로 연장한 감도분석에서 ICER는 1QALY당 30,012(천원), 6,620(천원), -10,054(천원)로 계산되었다. 결론: 5년을 기준으로 하여 한국인 류마티스관절염 환자에 있어 ETN의 조기사용전략은 현재의 일반적인 후기사용전략에 비해 비용효과비가 좋다고 할 수는 없는 것으로 나타났다. 그러나, 간접비용을 포함하거나 장기간의 사용이 필요할 경우에는 ETN의 조기사용전략의 비용효과비가 개선될 수 있을 것으로 판단된다.