Levels of blood glucose and hemoglobin A1c (HbA1c) are useful parameters to treat diabetes mellitus. However, daily fluctuations in blood glucose levels, as in postprandial hyperglycemia, nocturnal hypoglycemia, and silent hypoglycemia, are difficult to monitor. Daily glycemic variability is implicated in the onset of diabetes and progression of consequent. Flash glucose monitoring (FGM) system is the latest medical technology that can be used to keep track of daily glucose fluctuation, but FGM is not widespread because of limitations related to insurance coverage and other factors. Therefore, we investigated the safety of FGM using Free Style Libre Pro^® (Abbott Japan Co., Ltd.) to spread FGM into general clinics. This study was conducted on 50 patients with diabetes or borderline diabetes who wanted to use Free Style Libre Pro^® during outpatient visits. While using Free Style Libre Pro^®, 2 patients had uncomfortable sensation on the skin, when they came in contact with the sensor. There were no adverse events that were objective symptoms or subjective symptoms, such as itching or pain, in all patients. The systolic and diastolic blood pressure and pulse rate remained unchanged before and after using Free Style Libre Pro^® (130.48±14.84 mmHg vs 131.48±15.24 mmHg, p＝0.69; 73.48±10.36 mmHg vs 72.22±13.99 mmHg, p＝0.24; 82.34±13.60 bpm vs 82.92±11.91 bpm, p＝0.67, respectively). There was no significantly change in the levels of blood glucose and HbA1c (171.84±69.56 mg/dL vs 161.16±70.52 mg/dL, p＝0.15; 8.27±1.54％ vs 8.12±1.42％, p＝0.28, respectively).

These results showed that Free Style Libre Pro^® can be used safely at general clinics. The long-term results and accumulation of data are necessary for FGM to become a standard parameter of diabetes monitoring, like HbA1c, and to determine whether FGM is useful in improving the endpoints of diabetes.

Background: Digoxin has a narrow therapeutic window. A target serum digoxin concentration of ≤0.9 ng/mL is recommended for heart failure (HF). However, the appropriate serum digoxin concentration for HF patients with atrial fibrillation (AF) is not fully established. This study aimed to evaluate the relationship between the serum concentration and clinical outcome in patients with HF and AF receiving digoxin.

Methods: This single-center retrospective study included 348 patients with HF and AF receiving digoxin between 2008 and 2016 (median age, 68 years; female, 37％). The median follow-up period was 596 days. The clinical outcomes were all-cause death and digoxin intoxication. The patients were classified into 4 groups based on the digoxin trough concentration one month after the start of treatment: ＜0.60 ng/mL, 0.60-0.89 ng/mL, 0.90-1.19 ng/mL, and ≥1.20 ng/mL.

Results: The median digoxin dosage was 0.125 mg daily, and the median serum trough concentration of digoxin was 0.77 ng/mL. The incidence of all-cause death was not significantly different among the concentration groups. Multivariate analysis showed that serum digoxin concentrations ≥0.9 ng/mL were not associated with mortality. Using a modified Rosendaal linear interpolation method, the incidence of all-cause death did not increase with higher serum digoxin concentrations. Cardiac disturbance was observed in any of the concentration groups, but gastrointestinal symptoms were observed in patients with a serum digoxin concentration of ≥0.90 ng/mL.

Conclusions: Our results showed that all-cause death did not occur in a concentration-dependent manner in patients with HF and AF. Gastrointestinal symptoms due to digoxin intoxication but not cardiac disturbance increased with higher serum concentrations.

Background: Limited data are available to create an effective instruction strategy for clinical research coordinators (CRCs) based on their experience (years). We aimed to understand the association between the expertise level and experience of CRCs.

Methods: Data from a survey that developed a scale for evaluating the expertise level of CRCs were used. Pearson's coefficients of correlation were calculated to examine the association among the following four subscales: knowledge, basic skills, management skills and attitude, and experience (years). The mean scores on the subscales were compared among 5 groups categorized as per experience (years) using analysis of variance and multiple comparisons.

Results: Total 974 valid responses were received. Pearson's coefficient of correlation among the three subscales of knowledge, basic skill and management skill, and experience (years) was ≥0.5. The mean score of CRCs with ≥11 years of experience was 3.9/5 for knowledge, 4.5/5 for basic skills, 4.0/5 for management skills, and 4.0/5 for attitude. The mean scores for each subscale were significantly different for all five groups. However, there were no significant differences among several groups in multiple comparisons.

Conclusion: Knowledge, basic skills, and management skills of CRCs are associated with their professional experience (years). However, the basic skills do not improve after six years of experience; knowledge and management skills do not match those of an expert. Attitude is not associated with experience.

In September 2018, we introduced the Clinical Trial Document Support System (developed by the Center for Clinical Trials, Japan Medical Association) for document management of registration trials. Here we report the practical issues that we encountered in the introduction process and the evaluation of outcomes from the viewpoint of efficiency. However, the system was not intended for use in investigator-initiated clinical trials.

The practical issues encountered in the introduction process were examined. The outcomes of introduction of the system were evaluated by the following parameters: registration document width (to reduce space for document storage), number of site visits by monitors to confirm documents (to reduce correspondence time), cost of printing and disposal of documents for institutional review board members (to reduce cost for the trial site), and number of letters exchanged between the trial site and the sponsors (to reduce costs for the trial site and the sponsors).

Introduction of the system resulted in the reduction of average document width from 37.2 cm to 0.8 cm, number of site visits by monitors from 14 to 11, average cost for trial site from 34,970 yen to almost none, and average cost for both trial site and sponsors from 199,446 yen to 88,531 yen.

The analysis revealed that introduction of the Clinical Trial Document Support System contributed to increase the efficiency of management of registration trials. Further analysis is required to evaluate short- and long-term contributions of introduction of the system in various settings.

The United States of America (USA) is one of the leading countries that have been developing a program for patients with terminal illness to receive investigational treatments. In May 2018, President Trump signed into law the federal Right to Try Act (the federal RTT act). This law amends the Federal Food, Drug, and Cosmetic Act to allow more direct access to investigational drugs for patients with terminal illnesses who have exhausted available treatment options and who do not qualify for a clinical trial. There has been a huge controversy regarding the federal and state RTT acts in the USA because of their contents, such as the definition of eligible patients and drugs, ethical review, informed consent, safety monitoring, and incentives for pharmaceutical companies. The proponents of the RTT acts have stated that the existing expanded access program by the FDA has saved a limited number of patients due to the huge burden of documentation by physicians and the time-consuming review by the FDA. The opponents to the RTT acts have pointed out that the federal RTT act has done little to change pharmaceutical companies' practices compared to those under the expanded access program by the FDA. This paper aims to provide a history of the development of RTT acts in the USA and to understand the controversial points of the RTT pathway to receive investigational treatments.

In the pharmaceutical development, when a sponsor audits an external organization that has been contracted to clinically develop a pharmaceutical, the sponsor may have difficulty conducting the audit with their own resources given their lack of expertise in the contracted work. In the same vein, having an external organization undergo similar audits by multiple sponsors would presumably be inefficient. Thus, the current authors planned a “group audit” conducted jointly by multiple sponsors audited by the form entrusted an external organization, and the authors examined the usefulness of and issues with a group audit.

To select companies to undergo a group audit, authors conducted a questionnaire survey on Corporate members of the GCP Division of the Japan Society of Quality Assurance. Based on the results of the questionnaire survey, authors selected one laboratory testing company and one system vendor were obtained an agreement on acceptance of the group audit. This group audit involved a total of 22 companies. After the group audit, companies involved in the audit and companies being audited were surveyed, and assessments of the group audit and its advantages and disadvantages were examined. The main reasons why companies wanted to be involved in the group audit were because of “a lack of expertise in the area being audited” , “a lack of internal resources” , and “to reduce costs”.

The group audit received a more favorable rating overall than an individual audit, and respondents were highly satisfied with its “cost, effort, and quality” in particular. That said, the overall time taken for the audit was cited as one of its disadvantages.

Companies being audited rated the group audit as “no different from an individual audit”, and they considered “a group audit more acceptable”. These findings suggest that a group audit is a useful auditing approach, and this approach should increase the overall efficiency of auditing.

The quality of the outcome of clinical research is assured by being based on ICH-GCP requirements. An ICH-GCP-compliant data management system is required for participation in international joint research. Although ICH-GCP sets requirements for quality assurance, there are no specific criteria for data management. Therefore each academic research organization (ARO) data center has the responsibility to set criteria for its quality management system for clinical research. The European Clinical Research Infrastructure Network (ECRIN) has established specific requirements for IT system and data management in clinical research based on ICH-GCP and related regulations, and certifies non-commercial clinical trial units that meet the requirements. The ECRIN certification standards are feasible practical standards, and also applicable to data management of clinical research conducted by Japanese ARO. Besides, the ECRIN certification may also provide an indication of participation in global research, because the main activity of ECRIN is to promote and support the conduct of multinational clinical trials. Developing an ICH-GCP-compliant data management system utilizing the ECRIN Data Centre Certification Programme can improve the reliability of clinical research conducted in Japan or even promote participation in multinational clinical research. Thus we suggest to utilize the ECRIN Data Centre Certification Programme for the development of ICH-GCP-compliant data management system.