BACKGROUND: This study was aimed to investigate the current two years' clinical research coordinators (CRCs) employment and estimate total number of CRCs in Korea. METHODS: The participants were administrative officers or head CRCs in institutions designated by Korea Food & Drug Administration (KFDA). Data on the current status of CRCs' employment was collected with self-administered questionnaires or telephone interview. And total number of CRCs in Korea was estimated based on ratio between the number of the KFDA approved clinical trials and current number of CRCs. RESULTS: The number of CRCs was 1381 at 36 centers in 2009 and 1444 at 37 centers in 2010. About 79 percent of CRCs were employed by investigators. The estimated number of CRCs was from 1677 to 1763 at 135 centers in 2009 and from 1802 to 1890 at 142 centers in 2010 based on number of clinical trials approved by KFDA. Two third of regional clinical trial centers (RCTCs) had written employment policy, and 25 percent of RCTCs employed CRCs in a regular position. All RCTCs had educational programs for CRCs and supported CRCs for training outside. 75 percent of RCTCs provided ID card for CRCs belonging to investigators to access to hospital document. Half of RCTCs had CRC registration system in hospital-wide. CONCLUSION: The number of CRCs in Korea can be easily estimated with the number of KFDA approved clinical trials. Majority of RCTCs still employed CRCs in an irregular position, which should be switched to regular position to reduce the CRCs' unsatisfaction. It is also needed to develop centralized CRC management system for CRCs belonging to investigators.
Calcium Hydroxide ; Employment ; Head ; Humans ; Interviews as Topic ; Korea ; Surveys and Questionnaires ; Research Personnel ; Zinc Oxide

The purpose of this simulation study is to explore the limitation of the population PK/PD analysis using data from a clinical study and to help to construct an appropriate PK/PD design that enable precise and unbiased estimation of both fixed and random PD parameters in PK/PD analysis under different doses and Hill coefficients. Seven escalating doses of virtual drugs with equal potency and efficacy but with five different Hill coefficients were used in simulations of single and multiple dose scenarios with dense sampling design. A total of 70 scenarios with 100 subjects were simulated and estimated 100 times applying 1-compartment PK model and sigmoid E(max) model. The bias and precision of the parameter estimates in each scenario were assessed using relative bias and relative root mean square error. For the single dose scenarios, most PD parameters of sigmoid E(max) model were accurately and precisely estimated when the C(max) was more than 85% of EC₅₀, except for typical value and inter-individual variability of EC₅₀ which were poorly estimated at low Hill coefficients. For the multiple dose studies, the parameter estimation performance was not good. This simulation study demonstrated the effect of the relative range of sampled concentrations to EC₅₀ and sigmoidicity on the parameter estimation performance using dense sampling design.
Bias (Epidemiology) ; Clinical Study ; Colon, Sigmoid*

BACKGROUND: This study was aimed to investigate the perception on working conditions and utilization of clinical research coordinators (CRCs) among investigators and sponsors. METHODS: The participants of this cross-section study were 114 investigators and 138 sponsors including clinical research associates (CRAs) who have worked with CRCs. Data was collected with paper or electronic form of self-administered questionnaires and analyzed with descriptive statistics and chi2 test or t test. RESULTS: Among investigators and sponsors, 56.1 % and 95.0 % perceived regular full-time positions as proper type of CRC employment, respectively. Those who perceived monthly salary with incentive as proper payment system were 67.5 % of investigators and 68.8 % of sponsors. The proper salary for 2-year CRCs and 5-year CRCs were significantly higher in sponsors than investigators. Investigators perceived CRCs could handle 3 studies as the same time and 5 studies per year. In regard to the difficulty in utilizing CRCs, 68.4 % of investigators perceived lack of experienced CRCs and 84.8 % of sponsors did frequent turnover. Those who responded pooling CRCs by hospital or clinical trial centers as a good solution to hire CRCs easily were 81.6 % of investigators and 58.0 % of sponsors. CONCLUSION: Almost all investigators and sponsors perceived CRCs were helpful for improving the quality of clinical trials. We recommend each institution or clinical trial centers could introduce the central CRCs' employment and management with proper salary and workload based on the results to maintain experienced CRCs and lessen the turnover of CRCs.
Calcium Hydroxide ; Electronics ; Electrons ; Employment ; Humans ; Motivation ; Surveys and Questionnaires ; Research Personnel ; Salaries and Fringe Benefits ; Zinc Oxide

PURPOSE: Recently, the use of complementary and alternative medicine (CAM) is increasing among patients with low urinary tract symtoms (LUTS) caused by benign prostate hyperplasia (BPH). We assessed current usage and awareness of phytotherapy, the most ubiquitous CAM, in BPH/LUTS patients. MATERIALS AND METHODS: A total of 204 patients with BPH who completed a questionnaire between January 2009 and December 2010 were enrolled. The questionnaire was composed of questions about age, education level, accompanying disease, type of phytotherapy, route of purchase, reason of taking medicine and whether the patient is using phytotherapy in combination with conventional medicine. RESULTS: The mean age was 55.5+/-8.7 years. 56 of the total patients (27.5%) were using phytotherapy. The patients who were accompanied with erectile dysfunction used phytotherapy the most. The most commonly used phytotherapy for prescription and health functional food was Saw palmetto. The most common route of purchase was by clinician's prescription (46.4%). Most patients answered the dissatisfaction of present treatment's effect as the main reason for using phytotherapy. The number of patients who were taking combination therapy of BPH medication and phytotherapy was much more than using phytotherapy alone. CONCLUSIONS: 27.5% of patients who had BPH/LUTS were using phytotherapy. This is the point of time for many urologists to acquire the knowledge of studies and latest research of phytotherapy and use it in treating patients with BPH/LUTS.
Complementary Therapies ; Erectile Dysfunction ; Functional Food ; Herbal Medicine ; Humans ; Hyperplasia ; Lower Urinary Tract Symptoms ; Male ; Phytotherapy ; Prescriptions ; Prostate ; Prostatic Hyperplasia ; Surveys and Questionnaires ; Urinary Tract

BACKGROUND: Amlodipine is a third-generation dihydropyridine calcium channel blocker for treating hypertension. Though marketed primarily as a besylate salt, there have been some efforts to find other comparable salts. Among them, maleate is the salt that has been considered favorable for many drugs. The aim of this study was to compare the pharmacokinetics, as well as safety and tolerability of amlodipine maleate with amlodipine besylate. METHODS: This study was open, randomized, two-period crossover design investigated in twelve healthy male volunteers over a 144 h period after administrating two forms of amlodipine 5 mg, respectively. Each period was separated with 2 weeks. Plasma concentrations of amlodipine were determined by liquid chromatography-tandem mass spectrometry. Safety profiles were assessed by vital signs, physical examinations, electrocardiograms, laboratory testing and adverse events monitoring. RESULTS: All subjects were completed this study. Geometric mean ratios (GMRs) of amlodipine maleate/amlodipine besylate of Cmax and AUClast for amlodipine were 0.92 (90 % confidence interval, 0.81 ~ 1.05) and 1.05 (0.96 ~ 1.16), respectively. No serious adverse events were reported, and no clinically relevant changes were observed in safety profiles during this trial. CONCLUSION: Pharmacokinetics, tolerability and the safety were comparable between amlodipine maleate and amlodipine besylate in healthy individuals.
Amlodipine ; Calcium Channels ; Cross-Over Studies ; Dihydropyridines ; Electrocardiography ; gamma-Aminobutyric Acid ; Humans ; Hypertension ; Male ; Maleates ; Mass Spectrometry ; Physical Examination ; Plasma ; Salts ; Vital Signs

BACKGROUND: Amlodipine is a third-generation dihydropyridine calcium channel blocker, which has proven to be a useful drug against hypertension or angina. METHODS: This randomized, open-label, two-period, two-treatment, single-dose, crossover study was conducted in twenty healthy male volunteers. Subjects were administered 5 mg of the test or reference formulation. After 2-week washout period, the other formulation was administered. Blood samples were collected up to 144 hours after drug administration, and plasma amlodipine concentrations were determined by validated liquid chromatography-tandem mass spectrometry. Drug safety was assessed using measurement of vital signs, physical examinations, laboratory test, electrocardiograms, and adverse event monitoring. RESULTS: All subjects were completed this study. The geometric mean ratios of Cmax and AUClast were 1.078 (90 % CI, 0.968 - 1.200) and 1.095 (90 % CI, 1.011 - 1.186), respectively. There were no serious adverse events were reported by both formulations. CONCLUSION: This study showed the test and reference formulations had similar pharmacokinetics and safety profiles.
Amlodipine ; Calcium Channels ; Cross-Over Studies ; Electrocardiography ; Healthy Volunteers ; Humans ; Hypertension ; Male* ; Mass Spectrometry ; Pharmacokinetics ; Physical Examination ; Plasma ; Vital Signs

Indobufen (Ibustrin®), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using NONMEM® and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0–128 mg/L. Collagen-induced platelet aggregation in platelet-rich plasma was determined using a Chrono-log Lumi-Aggregometer. Inhibitory sigmoid I(max) model adequately described the anti-platelet effect. The S-form was more potent, whereas the R-form showed less inter-individual variation. No significant interaction was observed between the two enantiomers. The anti-platelet effect of multiple treatments with 200 mg indobufen twice daily doses was predicted in the simulation study, and the effect of S- or R-indobufen alone at various doses was predicted to define optimal dosing regimen for each enantiomer. Simulation study predicted that 200 mg twice daily administration of S-indobufen alone will produce more treatment effect than S-and R-mixture formulation. S-indobufen produced treatment effect at lower concentration than R-indobufen. However, inter-individual variation of the pharmacodynamic response was smaller in R-indobufen. The present study suggests the optimal doses of R-and S-enantioselective indobufen formulations in terms of treatment efficacy for patients with thromboembolic problems. The proposed methodology in this study can be applied to the develop novel enantio-selective drugs more efficiently.
Blood Platelets ; Colon, Sigmoid ; Healthy Volunteers ; Humans ; In Vitro Techniques ; Plasma ; Platelet Aggregation ; Platelet-Rich Plasma ; Treatment Outcome

The objective of this study was to externally validate a new dosing scheme for busulfan. Thirty-seven adult patients who received busulfan as conditioning therapy for hematopoietic stem cell transplantation (HCT) participated in this prospective study. Patients were randomized to receive intravenous busulfan, either as the conventional dosage (3.2 mg/kg daily) or according to the new dosing scheme based on their actual body weight (ABW) (23×ABW(0.5) mg daily) targeting an area under the concentration-time curve (AUC) of 5924 µM·min. Pharmacokinetic profiles were collected using a limited sampling strategy by randomly selecting 2 time points at 3.5, 5, 6, 7 or 22 hours after starting busulfan administration. Using an established population pharmacokinetic model with NONMEM software, busulfan concentrations at the available blood sampling times were predicted from dosage history and demographic data. The predicted and measured concentrations were compared by a visual predictive check (VPC). Maximum a posteriori Bayesian estimators were estimated to calculate the predicted AUC (AUC(PRED)). The accuracy and precision of the AUC(PRED) values were assessed by calculating the mean prediction error (MPE) and root mean squared prediction error (RMSE), and compared with the target AUC of 5924 µM·min. VPC showed that most data fell within the 95% prediction interval. MPE and RMSE of AUCPRED were -5.8% and 20.6%, respectively, in the conventional dosing group and −2.1% and 14.0%, respectively, in the new dosing scheme group. These fi ndings demonstrated the validity of a new dosing scheme for daily intravenous busulfan used as conditioning therapy for HCT.
Adult* ; Area Under Curve ; Behavior Therapy ; Body Weight ; Busulfan* ; Drug Dosage Calculations ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Pharmacokinetics ; Prospective Studies*

BACKGROUND/AIMS: Pancreatic cancer (PC) patients have poor prognoses because this cancer is typically diagnosed at an advanced stage and the therapeutic options are limited. We examined the potential of metabolic profiling for early diagnosis and identification of potential therapeutic targets. METHODS: Ten patients and 10 healthy volunteer controls older than 20 years of age were enrolled between May and December 2015. The patients were confirmed to have pancreatic ductal adenocarcinoma cytologically or histologically. Blood plasma samples were derivatized and analyzed by gas chromatography mass spectrometry (GC-MS). Untargeted GC-MS data were analyzed using statistical methods, including Wilcoxon rank-sum test and principal component analyses. RESULTS: L-lysine was 1.36-fold higher in patients than in healthy controls (p<0.05). L-leucine was 0.63-fold lower (p<0.01) and palmitic acid was 0.93-fold lower (p<0.5) in patients than in controls. Orthogonal partial least squared-discriminant analysis revealed significant differences between the patients and controls. CONCLUSIONS: This study suggests that the metabolic profiles of patients with PC are distinct from those of the healthy population. Further studies are required to develop methods for early diagnosis and identify therapeutic targets.
Adenocarcinoma ; Early Diagnosis ; Gas Chromatography-Mass Spectrometry ; Healthy Volunteers ; Humans ; Korea ; Leucine ; Lysine ; Metabolome ; Palmitic Acid ; Pancreatic Ducts ; Pancreatic Neoplasms ; Plasma ; Principal Component Analysis ; Prognosis

PURPOSE: We wanted to assess the clinical efficacy of breast-specific gamma imaging (BSGI) as compared with that of conventional imaging modalities (mammography, ultrasonography and magnetic resonance imaging) as a preoperative examination for patients with breast cancer. METHODS: From April to May 2009, a retrospective review was performed for the prospectively collected 143 patients who were diagnosed with breast cancer. All the patients received a conventional imaging examination and BSGI before definitive surgery. The patients underwent BSGI with intravenous injection of 30 mCi of (99m)Tc-sestamibi through the contralateral antecubital vein. After 10 minutes, the craniocaudal and mediolateral oblique images were obtained. All the imaging findings were correlated with the final pathologic examination. RESULTS: The mean age of the patients was 49.7+/-9.4 years (range, 27-77). In 143 patients, 166 malignant lesions were identified by pathologic examination (invasive cancer: 96 (67.1%), ductal carcinoma in situ 14 (9.8%) and invasive cancer with carcinoma in situ 33 (23.1%). The conventional imaging modalities found 166 malignant lesions and BSGI found 156 malignant lesions. The rate of correspondence was 94.0% between the conventional imaging modalities and BSGI for malignant lesions. For BSGI, there were 4 false positive findings and 10 false negative findings. BSGI found no occult cancers that were missed by conventional imaging modality. For making the diagnosis of axillary lymph node metastasis, the sensitivity, specificity and accuracy were 33.3%, 92.1%, and 69.9% for BSGI, and 55.6%, 77.5%, and 69.2%, for ultrasonography, respectively. CONCLUSION: BSGI may have the potentiality to make a correct diagnosis in breast cancer patients. However, in this study, it seems that BSGI is not superior to conventional imaging modalities. BSGI is not a standard method to evaluate breast cancer lesions before surgery.
Breast ; Breast Neoplasms ; Carcinoma in Situ ; Carcinoma, Intraductal, Noninfiltrating ; Gamma Cameras ; Humans ; Injections, Intravenous ; Lymph Nodes ; Magnetic Resonance Spectroscopy ; Neoplasm Metastasis ; Prospective Studies ; Retrospective Studies ; Sensitivity and Specificity ; Technetium Tc 99m Sestamibi ; Veins