The objective of this paper was to review the adherence and persistence rates of major antidiabetic medication classes (i.e., metformin, sulfonylureas, sodium glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, insulin, glucagon-like peptide-1 receptor agonists, and thiazolidinediones) by summarizing the major findings of the studies published since 2017. In addition, we reported the potential causes for low adherence and persistence of antidiabetic medications. Based on the literature, the highest rate of adherence and persistence was consistently observed in metformin users. Second to metformin were sodium glucose cotransporter-2 inhibitors. Injectable therapies such as insulin and glucagon-like peptide-1 receptor agonists trailed low on the adherence and persistence rates. To the best of our knowledge, no studies published since the year 2017 analyzed the adherence and persistence of thiazolidinediones independently. The most frequently cited cause for low adherence and persistence was the severity of adverse events. Baseline characteristics (e.g., baseline HbA1c level), demographic information (e.g., age, gender, or ethnicity), and comorbidity profiles also had significant impacts on adherence and persistence in patients with type 2 diabetes mellitus.

A low lymphocyte count puts immune‐compromised patients at risk of mortality. hIL‐7‐hyFc is a homodimeric interleukin‐7 (IL‐7), a potent T‐cell amplifier, fused to the hybridizing IgD/IgG4 immunoglobulin domain. We performed a randomized, double‐blind, placebo‐controlled, dose‐escalation, phase I study to assess the pharmacokinetic, pharmacodynamic, safety, tolerability, and immunogenicity profiles of hIL‐7‐hyFc administered s.c. and i.m. to healthy volunteers. Thirty subjects randomly received hIL‐7‐hyFc or its matching placebo in an 8:2 ratio at 20, 60 μg/kg s.c., or 60 μg/kg i.m. The hIL‐7‐hyFc was slowly absorbed and its terminal half‐life was 63.26 hours after i.m. administration. The hIL‐7‐hyFc increased absolute lymphocyte count, mostly in T‐cells, which peaked 3 weeks after administration and then lasted for several additional weeks. The hIL‐7‐hyFc was well‐tolerated after a single s.c. and i.m. administration. Injection site reaction was the most common treatment‐emergent adverse event, which resolved spontaneously without treatment. The hIL‐7‐hyFc can be developed into a beneficial treatment option for patients with compromised T‐cell immunity. This trial was registered at www.clinicaltrials.gov as #NCT02860715.

Since the outbreak of coronavirus disease 2019 (COVID-19) was first identified, the world has vehemently worked to develop treatments and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at an unprecedented speed. Few of the repositioned drugs for COVID-19 have shown that they were efficacious and safe. In contrast, a couple of vaccines against SARS-CoV-2 will be ready for mass rollout early next year. Despite successful vaccine development for COVID-19, the world will face a whole new set of challenges including scale-up manufacturing, cold-chain logistics, long-term safety, and low vaccine acceptance. We highlighted the importance of knowledge sharing and collaboration to find innovative answers to these challenges and to prepare for newly emerging viruses.

Determination of the starting dose in the first-in-human clinical trials with monoclonal antibodies: a systematic review of papers published between 1990 and 2013 Hoon Young Suh,1 Carl C Peck,2 Kyung-Sang Yu,1 Howard Lee1,3 1Department of Clinical Pharmacology and Therapeutics, College of Medicine, Seoul National University Hospital, Seoul, Korea; 2Department of Bioengineering and Therapeutic Sciences, School of Pharmacy, University of California, San Francisco, CA, USA; 3Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea A systematic review was performed to evaluate how the maximum recommended starting dose (MRSD) was determined in first-in-human (FIH) studies with monoclonal antibodies (mAbs). Factors associated with the choice of each MRSD determination method were also identified. PubMed was searched for FIH studies with mAbs published in English between January 1, 1990 and December 31, 2013, and the following information was extracted: MRSD determination method, publication year, therapeutic area, antibody type, safety factor, safety assessment results after the first dose, and number of dose escalation steps. Seventy-nine FIH studies with mAbs were identified, 49 of which clearly reported the MRSD determination method. The no observed adverse effects level (NOAEL)-based approach was the most frequently used method, whereas the model-based approach was the least commonly used method (34.7% vs 16.3%). The minimal anticipated biological effect level (MABEL)- or minimum effective dose (MED)-based approach was used more frequently in 2011–2013 than in 1990–2007 (31.6% vs 6.3%, P=0.036), reflecting a slow, but steady acceptance of the European Medicines Agency’s guidance on mitigating risks for FIH clinical trials (2007). The median safety factor was much lower for the MABEL- or MED-based approach than for the other MRSD determination methods (10 vs 32.2–53). The number of dose escalation steps was not significantly different among the different MRSD determination methods. The MABEL-based approach appears to be safer and as efficient as the other MRSD determination methods for achieving the objectives of FIH studies with mAbs faster. Keywords: MRSD determination method, starting dose in first-in-human study, first-in-human study with monoclonal antibody, MRSD, safety factor

Background: Failure mode and effects analysis (FMEA) is a risk management tool to proactively identify and assess the causes and effects of potential failures in a system, thereby preventing them from happening. The objective of this study was to evaluate effectiveness of FMEA applied to an academic clinical trial center in a tertiary care setting. Methods: A multidisciplinary FMEA focus group at the Seoul National University Hospital Clinical Trials Center selected 6 core clinical trial processes, for which potential failure modes were identified and their risk priority number (RPN) was assessed. Remedial action plans for high-risk failure modes (RPN >160) were devised and a follow-up RPN scoring was conducted a year later. Results: A total of 114 failure modes were identified with an RPN score ranging 3–378, which was mainly driven by the severity score. Fourteen failure modes were of high risk, 11 of which were addressed by remedial actions. Rescoring showed a dramatic improvement attributed to reduction in the occurrence and detection scores by >3 and >2 points, respectively. Conclusions: FMEA is a powerful tool to improve quality in clinical trials. The Seoul National University Hospital Clinical Trials Center is expanding its FMEA capability to other core clinical trial processes.