Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disease with cartilage destruction and bone erosions. Recently, many randomized controlled trials (RCTs) have shown that biologic response modifiers including tumor necrosis factor (TNF) inhibitors reduce disease activity and prevent tissue destruction. However, the results of RCTs may not be directly applicable to routine clinical practice because of the different situations including patient selection between RCTs and clinical practice, although the differences in patients' characteristics between RCTs and clinical practice have not been investigated in Japanese. In this study, we compared the demographic and disease characteristics of RA patients recruited in RCTs and those encountered in routine clinical practice.
We selected 52 patients who participated in RCTs of biologics or an anti-rheumatic drug that has been demonstrated to have comparable efficacy to biologics. As the comparator arm, 513 patients who were treated with TNF inhibitors (infliximab, etanercept, and adalimumab) or an IL-6 inhibitor (tocilizumab) in the outpatient clinic of Institute of Rheumatology, Tokyo Women's Medical University were selected. Demographic characteristics of the patients were not substantially different between two groups.In the analysis of disease characteristics, the disease severity assessed by disease activity score (DAS 28) and modified Health Assessment Questionnaire was not different between two groups. However, the proportion of patients treated with ≥7.5 mg/day prednisolone was significantly higher in RCTs than in routine clinical practice. Methotrexate dose was significantly higher in routine clinical practice than in RCTs. These results may reflect the differences in disease characteristics including comorbidities between patients recruited in clinical trials and those encountered in routine clinical practice.

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The Clinical Research Trial Network was established at the Ehime University Hospital in 2004, in collaboration with clinics in the western part of Shikoku Island. This is a network of clinics aiming at performing clinical trials on the same protocol at the same time. Ehime University Hospital provides education and training of investigators, clinical research coordinators (CRCs) and other staff for clinical trials, as well as review of protocols and informed consent documents used at the clinics participating in the network. From 2005, CRCs of Ehime University Hospital have started to visit the clinics of the network to support clinical trial activities and educate the staff. We assist the staff of the clinics in the storage of drugs and documents, in addition to support the procedures of informed consent and entry of volunteers. As a result, the number of clinical trials increased and the duration of trials was shortened. Visiting CRCs is useful to promote clinical trials in the region.

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The ‘Ethical Guidelines for Clinical Studies' of Japan, which was totally revised in 2008, requires the presidents of institutions to provide investigators engaged in clinical studies the opportunities to study about clinical research. Many institutions are considering to hold some in-house lecture meetings, but resources are usually limited. With the support from the Ministry of Health, Labour and Welfare Sciences Research Grant, we aimed to produce ‘easy-to-use’ training materials, especially for use in workshop style meetings and not for didactic lectures. We utilized the University hospital Medical Information Network-Clinical Trial Registry (UMIN-CTR) created by UMIN, and organized workshops in which the students experienced simulated registration of a clinical trial. We produced 7 mock protocols and explanatory materials used in post-exercise sessions. We tested one of the materials in three different institutions on students from various job categories including physician, nurse, and clerk. The questionnaire revealed that the materials and workshop style sessions at least helped beginners to become accustomed to clinical research.

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In kidney, the secretion of organic anions (OAs) takes place in the renal proximal tubular cells via at least two steps. The first is the transport of OAs from the blood across the basolateral membrane into the proximal tubules. The transport of p-aminohippurate (PAH), a prototypical substrate for the renal organic anion transport systems, across the basolateral membrane of proximal tubular cells against the electrochemical gradient occurs in exchange for intracellular dicarboxylates. Two organic anion transporters, OAT1 (SLC22A6) and OAT3 (SLC22A8), have been proposed to be responsible for this step. The second step is the exit of OAs across the apical membrane at the tubular epithelial cells into the urine. Voltage-driven organic anion transport plays an important role for this step. However, the molecular nature and precise functional properties of these efflux systems were largely unknown. Recently, the characteristics of human type I sodium-phosphate transporter hNPT4 (SLC17A3), an orphan transporter, has been analyzed using Xenopus oocyte expression system. hNPT4 acts as a voltage-driven transporter for several OAs such as PAH, estrone sulfate, diuretic drugs and urate. This finding will complete a model of the secretion of OAs in the renal tubular cell, where OAs in the blood are taken up via OAT1 and/or OAT3 and intracellular OAs exit from the cell into the tubular lumen via hNPT4.

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