Nearly 3 years after the emergence of COVID-19, it remains one of the world's problems. COVID-19 vaccination is a priority programme for reducing death and severe symptoms. The primary recombinant novel coronavirus ZF2001 vaccine has gone through Phase III clinical trials and demonstrates efficacy against the highly critical COVID-19 globally and in Indonesia (87.6% and 76.0%, respectively). This study aimed to assess immune persistence after three doses of ZF2001. The study monitored and followed up 400 participants 14 days and 6 months after the third dose and investigated immune persistence 6 months after the phase III vaccination (ZF2001). This study was conducted at recruitment locations in Bandung. Participants were divided into the vaccine and placebo groups and entered into the immunogenicity group. The immune persistence of the vaccine was assessed by measuring geometric mean titres (GMT), neutralising antibodies and seropositivity of IgG anti-S-receptor-binding domain (RBD) after 14 days and 6 months. The seropositive antibody rates were nearly the same between 14 days and 6 months. After 6 months, the GMT, seropositivity of IgG anti-S-RBD and neutralising antibodies in the vaccine group decreased significantly, from 6447.63 to 1514.61 with a P-value of 0.001. A booster was considered important after 6 months.

The entire clinical trial process is a perfectly orchestrated team. It took many years before centers started hiring clinical trial coordinators. The centers that decided to do so noted not only positive aspects from the technical side of the study, but also from the side of the participants -which are the patients. The aim of the publication was to collect literature data showing the work of the coordinator in the centers and its impact on increasing the effectiveness of the study. The comparison additionally included the importance of the coordinator's role on patient recruitment and perceptions. The centers analyzed, showed the impact of the coordinator on their center's research at approximately: 99.1% in China (knowledge of patient rights), 80% in Italy (increasing the quality of the clinical trial conducted) and 70% in South Korea (impact on reducing patient withdrawal of consent). Those teams that worked without the support of a coordinator gained less trust among patients, which affected recruitment and retention of participants. The coordinator's influence on study management resulted in better organization of the study. Conclusions reached can support the development of centers and thus clinical trials around the world. Hiring a coordinator not only has an impact on improving the management of the study, but also on increasing the number of patients included, and thus increasing the therapeutic options in medicine. This paper aims to compile existing literature concerning the responsibilities of clinical trial coordinators and subsequently advocate for the value they bring to enhancing the efficacy and efficiency of clinical trials.

Weichung J Shih,1 Xin Shen,2 Peng Zhang,2 Tai Xie2 1Rutgers University School of Public Health, Piscataway, NJ 08854, USA; 2CIMS Global, Somerset, NJ 08873, USACorrespondence: Weichung J Shih Email shihwj@sph.rutgers.eduIntroduction: The first clinical trial on remdesivir for treatment of severe COVID-19 conducted in China was terminated prematurely due to limited patient enrollment, which rendered the findings inconclusive. We re-analyzed the efficacy with a statistically more powerful and clinically meaningful method based on published data using the 6-point ordinal scale of patient’s disease severity.Methods: We defined response as patient’s point reached, either 2 (hospitalized, no requirement for supplementary oxygen therapy) or 1 (discharged or met discharge criterion), and then analyzed with logistic regression with baseline score, day of assessment, treatment group, baseline by treatment interaction, and day by treatment interaction as covariates. The binary endpoint was supported by the recent FDA’s guidance on COVID-19.Results: Eighty-two percent (82%) of the patients were in the disease severity point=3 (hospitalized, required supplemental oxygen (but not NIV/HFNC)) – the moderately severe category. The response rate was 85% for remdesivir-treated patients with baseline disease point=3 versus 70% response rate for likewise placebo-treated patients on Day 28 (OR=2.38, P=0.0012). On Day 14, the response rate for these patients was 43% for remdesivir versus 33% for placebo (OR=1.53, P=0.0022). For patients with baseline disease point=4 (critically severe category), no similar comparisons were statistically significant.Conclusion and Discussion: The Chinese trial was not really under-powered as previously perceived or portrayed by many opinions. This result supports the preliminary findings of ACTT that remdesivir is effective for patients who were not critically severe. This result also suggests that remdesivir should be given to hospitalized COVID-19 patients as soon as possible. There is no race difference in the treatment effect.Keywords: COVID-19, novel coronavirus, remdesivir

Background: The fraction of patients participating in clinical research studies has been relatively low and declined further in recent years, and many barriers are facing healthcare providers in conducting such studies. Our aim in this study is to identify common barriers facing our healthcare providers to conduct clinical trials in those patients in the MENA region. Methods: A qualitative study was carried out between July 2014 and April 2015 where the semistructured survey was conducted using Survey Monkey software to all healthcare providers who work in seven different domain areas (physicians, pharmacists, nurses, clinical research associates, clinical research coordinators, auditors, and IRB members and data entry clerks). Results: Of 329 responders from 7 specialties, the majority [183 (55.62%)] were males and 193 (58.66%) from Saudi Arabia. Physicians and pharmacists represent the majority [155 (47.11%) and 76 (23.10%)] of the total group, respectively, and the least were nurses and auditors [5 (1.52%) in each]. The highest rate barrier reported by physicians and pharmacists was inadequate training in clinical research implementation [76 (23.1%)], while clinical research coordinator reported the same barrier in 18 (5.5%). Clinical research associates reported a lack of incentive and credit for research work in 17 (5.2%). Reviewers reported a lack of leadership support and lack of financial grant support [5 (1.5%)] for both. The top reported strength points were having an opportunity for professional development [96 (29.2)] and being in an academic institution [97 (29.5)]. Of the total participants, 200 (60.79) of the participants suggested the need for more training on research methodology. Conclusion: This study demonstrated the barriers that face healthcare providers in the MENA region. Because of the inadequate training in clinical research implementation and the lack of designed system operating procedures for the research process, we should address to facilitate clinical research in the region. Keywords: clinical research in Arabic countries, barriers to participating, attitude, conducting research studies

Introduction: The informed consent process is a fundamental part of clinical trials and is driven by both a legal and ethical agenda. The process may be seriously compromised if trial participants sign the informed consent document without fully understanding its contents. In developing countries such as South Africa, this concern is important due to the potential vulnerability of these patients and their risk for research exploitation. Aim: To evaluate the understanding of 11 important components and concepts related to clinical research by adult trial participants in a developing country at the time of providing consent for trial participation. Methods: 46 consecutive adult patients who qualified and consented to being enrolled in ongoing cardiovascular risk clinical trials at TREAD Research in the Western Cape, South Africa, were included in this study. After giving informed consent, participants were subjected to both a close-ended (self-report) and an open-ended method (descriptive narrative) to assess their understanding of various components and concepts related to clinical research pertaining to the initial informed consent document. The descriptive narrative was recorded and then later transcribed and assessed by two independent assessors. Results: There was a marked difference between the two methodologies used to assess patient comprehension of the various components. With the exception of concepts voluntariness and right to withdraw, trial participants’ understanding of the informed consent document was poor – especially with regard to the following concepts: randomization, risks, placebo and blinding. Higher levels of comprehension were obtained for the participant self-reports and lower levels for the narrative descriptions. Conclusion: The participant comprehension at this site was poor, and the process for taking informed consent subsequently needs to be modified so as to improve informed consent comprehension. Keywords: clinical trials, informed consent comprehension

Introduction: The purpose of the secondary analysis of the data from the clinical trial “A Study to Evaluate Efficacy of IP on Alertness and Mental Fatigue” (ClinicalTrials.gov NCT02816827) was to investigate the effect of the Alpinia galanga proprietary extract E-AG-01 (EnXtra) on focused attention, in comparison with caffeine and placebo in moderate caffeine habitués. Participants and methods: A total of 59 caffeine-habituated healthy young adults (aged 18–40 years) with body-mass index of 18.5–25.0 kg/m 2 were crossed over in four interventional groups: placebo, E-AG-01, caffeine, and a combination of caffeine and E-AG-01. All participants completed the attention-network test, which measures the accuracy and speed factors of the alerting, orienting, and executive-control networks. Results: The results of accuracy parameters in terms of percentage-error rate showed a remarkable difference between E-AG-01 and the other treatment groups, wherein the error rate dropped by 1.63% (1 hour), 1.32% (3 hours), and 0.78% (5 hours) from baseline. The caffeine group demonstrated a decrease of 0.37% (1 hour) and 0.44% (3 hours), followed by an increase of 0.2% (5 hours), whereas the error rate of subjects in the caffeine + E-AG-01 group decreased by 0.24% (1 hour) and 0.26% (3 hours), followed by an increase of 0.2% at 5 hours. The placebo group exhibited an increase of 0.14% (3 hours) and 0.77% (5 hours). Conclusion: These results show that E-AG-01 exhibited selectively enhanced focused attention to a higher extent in comparison with caffeine and placebo. Keywords: accuracy, ANT, dietary supplement, error rate, energy drink, EnXtra, clinical trial

Purpose: The Food and Drug Administration (FDA) permits investigators to withhold active interventions from human subjects randomly assigned to control groups in clinical trials. The scope of this practice in trials for life-threatening diseases is unknown. We assessed the frequency and characteristics of trials providing control group subjects with active interventions versus those providing only placebos to control group subjects in trials supporting FDA approvals of new drugs for nine life-threatening diseases. Materials and methods: We reviewed the FDA’s database of approved drug products and identified all new approvals from 2006 to 2011 for drugs or biological products indicated for asthma, bipolar disorder, chronic obstructive pulmonary disease (COPD), diabetes mellitus, hypertension, osteoporosis, Parkinson’s disease, partial seizures, and schizophrenia. Then, we identified all trials described in FDA medical review documents for these approvals and abstracted information on trial characteristics and the interventions provided to control group subjects. Results: Of 508 included trials, 201 (39.6%) were placebo-only-controlled, meaning subjects in at least one control group did not receive an active intervention, and 307 (60.4%) were active-controlled, meaning subjects in all control groups received an active intervention. The total recorded enrollments in control groups provided with placebos only and in control groups provided with active interventions were 19,361 and 93,093 subjects, respectively. The proportion of placebo-only-controlled trials varied across diseases ( P <0.001), ranging from 75.5% for COPD to 0% for partial seizures and osteoporosis. Placebo-only controls were used in 76.9% of trials for severe COPD, 56.4% of trials for severe hypertension, 43.8% of trials for moderate or severe persistent asthma, and 6.7% of trials for severely uncontrolled diabetes. Logistic regression analysis showed that longer trials were associated with lower odds of being placebo-only-controlled compared with shorter trials. Conclusion: Providing only placebos to control groups in trials for life-threatening diseases is a common practice, potentially entailing varying degrees of risk to subjects. Further research is warranted to assess the impact of this practice, particularly in trials of long duration and those involving subjects with severe disease. Keywords: drug approval, bioethics, medical ethics, Food and Drug Administration, research ethics

Randomized response surface pathway design with odd response outcomes in a Latin Square designed study Trond Holand,1 Kristian Ellingsen,2 Sagita Dewi,1,3 Stig Larsen1 1Centre for Epidemiology and Biostatistics, Department of Production Animal Clinical Sciences, Faculty of Veterinary Science, Norwegian University of Life Science, 2Norwegian Veterinary Institute, Oslo, Norway; 3Bali Indera Hospital, Government of Bali Province, Denpasar, Bali, Indonesia Background: Response surface pathway (RSP) design has been recently developed and described for dose-finding studies. The aim of this paper was to introduce and demonstrate additional procedures to strengthen and generalize the design and combine RSP with classical study design.Materials and methods: Nine bull calves and six heifer calves were included in an unbalanced 2&nbsp;&times;&nbsp;2 Latin Square (LSQ) designed study with large and small aperture bottle teats. The two LSQ sequences were performed with independent randomized three-level between-patient RSP design with an odd number of response classifications. The milk temperature window was 8&deg;C&ndash;38&deg;C with a mid temperature of 23&deg;C. X-rays of the abdominal cavity were taken before, during, and immediately after intake of milk and recorded as &ldquo;milk&rdquo;, &ldquo;trace&rdquo;, or &ldquo;no milk&rdquo;. Based on the results of the first design level, the milk temperatures for five calves in the second design level were obtained by a randomization procedure. A similar procedure was performed for seven calves in the third design level. Adjustment of the dose from one design level to the next was based on a k-adjustment factor estimated to ensure coverage of the entire predefined dose window.Results: Starting with a low number of subjects and increasing this number with increasing design levels reduces the sample size without reducing the power. The suggested randomization procedure worked as expected. No milk in Rumen was recorded and minimum milk temperature (MMT) was estimated to be &le;8&deg;C for both teats. The odd number of response categories increases the flexibility of RSP, enabling category redefinition in hindsight from &ldquo;trace&rdquo; to &ldquo;uncertain&rdquo;. After category redefinition, MMT for large bottle teat was estimated to be 14.3&deg;C (95% confidence interval: 8.3&ndash;20.3&deg;C), but 8&deg;C for small.Conclusion: The suggested changes and additional procedures increase the strength and flexibility of the RSP design. Keywords: k-adjustment factor, Latin Square design, patient reduction in clinical trials, randomized response surface pathway design

Purpose: Patients in the intensive care unit (ICU) are at an increased risk for medication errors (MEs) and adverse drug events from multifactorial causes. ME rate ranges from 1.2 to 947 per 1,000 patient days in the medical ICU (MICU). Studies with the implementation of electronic health records (EHR) have concluded that it significantly reduced overall prescribing errors and the number of errors that caused patient harm decreased. However, other types of errors, such as wrong dose and omission of required medications increased after EHR implementation. We sought to compare the number of MEs before and after EHR implementation in the MICU, with additional evaluation of error severity. Patients and methods: Prospective, observational, quality improvement study of all patients admitted to a single MICU service at an academic medical center. Patients were evaluated during four periods over 2 years: August–September 2010 (preimplementation; period I), January–February 2011 (2 months postimplementation; period II), August–September 2012 (21 months postimplementation; period III), and January–February 2013 (25 months postimplementation; period IV). All medication orders and administration records were reviewed by an ICU clinical pharmacist and ME was defined as a deviation from established standards for prescribing, dispensing, administering, or documenting medication. The frequency and classification of MEs were compared between groups by chi square; p <0.05 was considered significant. Results: There was a statistically significant increase in the number of MEs per 1,000 patient days during time periods II (N=2,592; p <0.001) and III (N=2,388; p =0.0023) compared to baseline (N=1,972). However, over time there was a significant reduction in medication errors during period IV compared to baseline (N=1,669; p =0.0008). Conclusion: In the short-term, EHR did not lead to a reduction in medication errors in the ICU; however, there was a significant decrease in medication errors after 2 years. Keywords: electronic health record, intensive care unit, medication error, patient safety, computerized physician order entry, quality improvement

An international, multicenter, observational survey to evaluate diabetes control in subjects using insulin for the treatment of type 1 and type 2 diabetes mellitus in the Czech Republic and Slovak Republic: study protocol for a cross-sectional survey Jan Brož,1 Denisa Janickova Zdarska,1 Jana Urbanova,2 Marek Brabec,3 Bohumila Krivska,4 Viera Donicova,5 Radka Stepanova,6 Emil Martinka,7 Milan Kvapil1 1Department of Internal Medicine, Second Faculty of Medicine, 2Center for Research on Diabetes, Metabolism and Nutrition, Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, 3Institute of Computer Science of the ASCR, vvi, 4Sanofi, Prague, Czech Republic; 5Private Department of Diabetology, Internal Medicine and Metabolism, Kosice, Slovak Republic; 6ADDS sro, Brno, Czech Republic; 7National Institute of Endocrinology and Diabetology, Lubochna, Slovak Republic Background: Despite the improvements in insulin therapy, a large number of patients fail to achieve their target glycated hemoglobin (HbA1c) levels. Control of diabetes is often unsatisfactory because the patient does not know about the principles of successful insulin therapy (ie, blood glucose self-monitoring, the principles of insulin administration, titration, current dose adjustments, dietary recommendations, and physical activity preventive measures) or because these principles are applied incorrectly or insufficiently. Furthermore, the fear of hypoglycemia may lead to maintaining higher than recommended blood glucose levels. Methods/design: This is a noninterventional, international study focusing on a questionnaire survey of diabetes patients (patient-reported outcome) treated with insulin for at least 1 year. It is designed so that the data obtained reflect real access of patients to insulin treatment. The primary objective is to show the results of glycemic control of diabetes (HbA1c) achieved in diabetes patients treated with at least one dose of insulin. The secondary objective is to monitor the factors potentially affecting these results, which include the frequency and other characteristics of hypoglycemia, the frequency of blood glucose self-monitoring, and the effects produced when the results are employed in adjusting the therapy. Furthermore, the study investigates factors related to the principles of insulin administration, dietary regime, and exercise habits. The study will enroll a total of 1,500 patients with type 1 and type 2 diabetes in 150 centers: two-thirds in the Czech Republic and one-third in the Slovak Republic. Discussion: The study is primarily aimed at determining the percentage of insulin-treated diabetes patients reaching the recommended targets for glycemic control (HbA1c). Furthermore, it attempts to identify and describe in detail the factors of failure in achieving the therapeutic goals. An analysis of the data thus obtained may result in recommendations on how to reduce and eliminate all the identified negative factors in the future. Keywords: insulin therapy, glycemic control, HbA1c, hypoglycemia, education, diabetes regimen adherence