Good Clinical Practice Guidelines Research Articles

A phase 1/2 study of EG-70 (detalimogene voraplasmid) intravesical monotherapy for patients with BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ.

TPS4626 Background: High-risk non-muscle-invasive bladder cancer (NMIBC) is treated with adjuvant intravesical Bacille Calmette-Guérin (BCG). However, approximately 50% of patients experience recurrence and/or progression after BCG treatment and are considered unresponsive. EG-70 (detalimogene voraplasmid) is an investigational drug product that was specifically engineered for intravesical administration to elicit local stimulation of anti-tumor immune responses in the bladder and drive durable efficacy in patients with BCG-unresponsive NMIBC, while mitigating the risk of systemic toxicities from immune stimulation. The phase 1 (dose-escalation) part of the first-in-human LEGEND (NCT04752722) phase 1/2, open-label, multicenter study of EG-70 in patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) is complete: intravesical instillation of EG-70 was well tolerated with an overall complete response (CR) rate of 73%; and the recommended phase 2 dose (RP2D) was identified. Here we describe the ongoing phase 2 part of the study, which opened to enrollment in May 2023. Methods: Patient eligibility criteria: age ≥18 years; ECOG PS 0−2; BCG-unresponsive NMIBC with CIS, with or without resected coexisting papillary tumors, ineligible for, or have elected not to undergo, cystectomy; satisfactory bladder function with ability to retain study drug for ≥60 minutes. Prior checkpoint inhibitor treatment is allowed if completed within 30 days before study entry. Patients are treated with EG-70 at the RP2D (800 µg in 50 mL) by intravesical administration on weeks 1, 2, 5, and 6 of a 12-week cycle, for 4 cycles in one of two cohorts: BCG-unresponsive (Cohort 1); BCG-naïve or BCG-incompletely treated (Cohort 2). Patients in either cohort who exhibit stable disease (SD) or CR at week 12 will continue treatment until week 24; patients with progressive disease (PD) will discontinue treatment. Patients who experience or maintain CR at week 24 will receive additional cycles every 12 weeks until week 48; patients with SD or PD at week 24 will discontinue treatment. Patients with PD at any time after week 24 will discontinue treatment. Phase 2 primary objective: evaluate efficacy (CR rate at week 48) and safety of EG-70. Secondary objectives: evaluate progression-free survival, CR rate at 12, 24, 36 and 48 weeks, and duration of response. The study is being conducted in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines and with the principles of the Declaration of Helsinki. All patients provide written informed consent. The ongoing, registration-enabling phase 2 portion of the LEGEND study is anticipated to recruit approximately 100 patients from sites in North America, Europe, and the Asia-Pacific region. Clinical trial information: NCT04752722 .

Disease characteristics, effectiveness, and safety of vestronidase alfa for the treatment of patients with mucopolysaccharidosis VII in a novel, longitudinal, multicenter disease monitoring program

BackgroundMucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of β-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII.MethodsThis disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (N ≈ 50 planned) treated with vestronidase alfa or any other management approach. Data are monitored and recorded in compliance with Good Clinical Practice guidelines and planned interim analyses of captured data are performed annually. Here we summarize the safety and efficacy outcomes as of 17 November 2022.ResultsAs of the data cutoff date, 35 patients were enrolled: 28 in the Treated Group and seven in the Untreated Group. Mean (SD) age at MPS VII diagnosis was 4.5 (4.0) years (range, 0.0 to 12.4 years), and mean (SD) age at DMP enrollment was 13.9 (11.1) years (range, 1.5 to 50.2 years). Ten patients (29%) had a history of nonimmune hydrops fetalis. In the 23 patients who initiated treatment prior to DMP enrollment, substantial changes in mean excretion from initial baseline to DMP enrollment were observed for the three urinary glycosaminoglycans (uGAGs): dermatan sulfate (DS), -84%; chondroitin sulfate (CS), -55%; heparan sulfate (HS), -42%. Also in this group, mean reduction from initial baseline to months 6, 12, and 24 were maintained for uGAG DS (-84%, -87%, -89%, respectively), CS (-70%, -71%, -76%, respectively), and HS (+ 3%, -32%, and − 41%, respectively). All adverse events (AEs) were consistent with the known vestronidase alfa safety profile. No patients discontinued vestronidase alfa. One patient died.ConclusionsTo date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing.

A Brief Review on Good Clinical Practice and its Training Methods

Abstract The field of clinical research continues to advance, and for ethical conduct of research, researchers need to have a strong foundation in good clinical practice (GCP). GCP guidelines are internationally recognized standards that govern the conduct of clinical trials, ensuring the protection of human subjects and the generation of reliable data. However, novice researchers or postgraduate medical students who would delve into research activities may face difficulty getting avenues for GCP training. Hence, in this brief review article, we discuss the significance of GCP in the field of clinical research with a glimpse of its history, development, and key principles. We provide a list of online courses, benefits, and disadvantages of those courses, and a list of organizations that conduct GCP workshops or continued medical education programs in India.

Recommendations for the Clinical Development of Medicinal Products for Non-specific Influenza Chemoprophylaxis

INTRODUCTION. The evolution of the influenza virus has led to a gradual decrease in the effectiveness of current antivirals. Better methods of prevention, detection, control, and treatment of influenza are needed, including more effective vaccines and antivirals. At the moment, the Russian Federation and the Eurasian Economic Union lack documents regulating the conduct of clinical trials of medicinal products for influenza prevention and require that guidelines should be developed for the matter.AIM. The authors aimed to analyse the main regulatory approaches to preclinical and clinical development programmes for medicinal products for influenza prevention in the Russian Federation, the Eurasian Economic Union (EAEU), the European Union, and the United States of America.DISCUSSION. This review substantiates the importance of non-specific influenza chemoprophylaxis in reducing the risk of adverse outcomes of the disease. The authors analysed the main stages of preclinical development of medicinal products for influenza prevention and the potential contribution of preclinical studies to the planning of clinical trials. When developing preclinical and clinical programmes for medicinal products for influenza prevention, it is necessary, first of all, to take into account the requirements of the national good clinical practice guidelines and the EAEU guidelines for clinical trials in general. This article pays particular attention to the clinical trial designs used internationally, the possible options for their implementation, the characteristics of study populations, the formation of study groups, and the selection of primary and secondary endpoints.CONCLUSIONS. The article proposes approaches to planning and conducting clinical trials of medicinal products for the prevention of influenza, taking into account the specifics of legal norms and clinical traditions of Russian practice. These recommendations will ensure high-quality data on the effectiveness and safety of investigational medicinal products and accelerate the introduction of new effective medicinal products for influenza prevention into medical practice.

Home-based Intervention with Semaglutide Treatment of Neuroleptic-Related Prediabetes (HISTORI): protocol describing a prospective, randomised, placebo controlled and double-blinded multicentre trial

IntroductionSubjects with schizophrenia have a 2–3 fold higher mortality rate than the general population and a reduced life expectancy of 10–20 years. Approximately one-third of this excess mortality has been...

임상시험연구 교과기반 학습성과 평가

Objectives The purpose of this study is to evaluate the awareness of ethical perspective and clinical research coordinator's roles in an entry-level clinical trial research course based on the course-embedded assessment tied with the program learning outcomes of the bachelor's degree among nursing students.
 Methods Three professional clinical coordinators affiliated with Korea National Enterprise for Clinical Trials (KoNECT) and two nursing professors developed the course based on Good Clinical Practice guidelines in clinical trials. Eighty-three nursing students enrolled and completed this course. Three evaluation criteria were rated in the course-embedded assessment: Completion of the course by getting certificate from the KoNECT(70%), attendance (10%), reflection journal report (20%). Additionally, learners responded two surveys on the satisfaction with education and awareness of ethical roles in clinical trial research. Data were analyzed using the SPSS 23.0 program. The difference in ethical awareness of clinical trial research according to general characteristics was analyzed using t-test and ANOVA with Scheffé's multiple comparison. Importance-Performance analysis(IPA) and thematic analysis were used for ethical perspective and the clinical research coordinator's roles.
 Results All students completed the clinical trial research course by getting the KoNECT certificates, and 94% of students reported that they were satisfied with the course. IPA analysis showed that nursing students recognized all the ethical roles of clinical trial research nurses as more important and more performing. Thematic analysis exhibited that the roles of CRC had four main themes: expertise and responsibility as clinical trial specialists, decision-making based on ethical principles, sufficient education and explanation for the voluntary participation of subjects, and the convergent capability underlying clinical trial research.
 Conclusions Based on these findings, the entry-level clinical trial research course was useful for developing awareness of ethical roles and CRC's roles, and provided a new opportunity to map out nursing students' career path.

Impact of intraosseous regional administration of tranexamic acid in total knee arthroplasty on perioperative blood loss: a protocol for a randomised controlled trial

IntroductionTotal knee arthroplasty (TKA) is a common surgical intervention to treat joint diseases. However, TKA is associated with significant blood loss. Tranexamic acid (TXA) has been used to reduce perioperative...

Predicting mortality risk in hospitalized COVID-19 patients: an early model utilizing clinical symptoms

BackgroundDespite global efforts to control the COVID-19 pandemic, the emergence of new viral strains continues to pose a significant threat. Accurate patient stratification, optimized resource allocation, and appropriate treatment are crucial in managing COVID-19 cases. To address this, a simple and accurate prognostic tool capable of rapidly identifying individuals at high risk of mortality is urgently needed. Early prognosis facilitates predicting treatment outcomes and enables effective patient management. The aim of this study was to develop an early predictive model for assessing mortality risk in hospitalized COVID-19 patients, utilizing baseline clinical factors.MethodsWe conducted a descriptive cross-sectional study involving a cohort of 375 COVID-19 patients admitted and treated at the COVID-19 Patient Treatment Center in Military Hospital 175 from October 2021 to December 2022.ResultsAmong the 375 patients, 246 and 129 patients were categorized into the survival and mortality groups, respectively. Our findings revealed six clinical factors that demonstrated independent predictive value for mortality in COVID-19 patients. These factors included age greater than 50 years, presence of multiple underlying diseases, dyspnea, acute confusion, saturation of peripheral oxygen below 94%, and oxygen demand exceeding 5 L per minute. We integrated these factors to develop the Military Hospital 175 scale (MH175), a prognostic scale demonstrating significant discriminatory ability with an area under the curve (AUC) of 0.87. The optimal cutoff value for predicting mortality risk using the MH175 score was determined to be ≥ 3 points, resulting in a sensitivity of 96.1%, specificity of 63.4%, positive predictive value of 58%, and negative predictive value of 96.9%.ConclusionsThe MH175 scale demonstrated a robust predictive capacity for assessing mortality risk in patients with COVID-19. Implementation of the MH175 scale in clinical settings can aid in patient stratification and facilitate the application of appropriate treatment strategies, ultimately reducing the risk of death. Therefore, the utilization of the MH175 scale holds significant potential to improve clinical outcomes in COVID-19 patients.Trial registrationAn independent ethics committee approved the study (Research Ethics Committee of Military Hospital 175 (No. 3598GCN-HDDD; date: October 8, 2021), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.

Pragmatic Adaptive Trial for Respiratory Infection in Children (PATRIC) Clinical Registry protocol

IntroductionAcute respiratory infections (ARI) are the most common cause of paediatric hospitalisation. There is an urgent need to address ongoing critical knowledge gaps in ARI management. The Pragmatic Adaptive Trial...

‘Effects of a home-based bimodal lifestyle intervention in frail patients with end-stage liver disease awaiting orthotopic liver transplantation’: study protocol of a non-randomised clinical trial

IntroductionPatients with end-stage liver disease awaiting orthotopic liver transplantation (OLT) are generally classified as frail due to disease-related malnutrition and a progressive decline in musculoskeletal and aerobic fitness, which is...

Evaluation of knowledge and awareness of clinical trials among undergraduate, interns, and postgraduate medical students

Background: Clinical trials aim to improve health care by reducing treatment costs, enhancing quality, and advancing the discovery of safe treatments. Notably, limited knowledge among resident doctors may impact research quality. Aims and Objectives: The study seeks to evaluate awareness and knowledge of clinical trials among undergraduate, intern, and postgraduate medical students. Materials and Methods: It was an observational, cross-sectional study conducted on 300 medical students over 3 months after approval from the Institutional Ethics Committee (IEC). The pre-validated questionnaire containing 24 items was administered through email, WhatsApp, or in person. Data were analyzed using descriptive statistics. Results: In the study, 96.7% of participants believe the necessity of clinical trials. Notably, 72% of undergraduates and 76% of postgraduates express willingness to participate in a clinical trial. Furthermore, 93% of participants view trials as vital for innovative therapies, and 74.3% believe that they enhance health-care services. Knowledge gaps in clinical trials were evident: 56.3% of participants knew good clinical practice guidelines, 46.7% of participants were aware of them, and only 12.3% of participants knew the IEC role. However, 66.7% of participants recognized the Drug Controller General of India (DCGI) and IEC approvals as crucial for trials, and 53.7% of participants identified DCGI as the regulatory authority. 68.3% of participants could not define a placebo-controlled trial. However, 75% of participants were aware of the consequences of informed consent form non-compliance. Most knew about post-marketing surveillance (80.33%), but awareness of healthy volunteer involvement in Phase 1 was lower (48%). In addition, 62.33% of participants knew about marketing access after Phase 3, and 60% of participants were aware of adverse effects reporting procedures. Conclusion: The study reveals a concerning lack of awareness regarding clinical trials among undergraduate, intern, and postgraduate medical students, emphasizing the need for targeted educational interventions in medical curricula.

Compliance challenges in clinical research organizations: A USFDA inspection retrospective

Context: Clinical research plays a vital role in advancing medical knowledge and improving patient care. As regulatory bodies strive to ensure the integrity and safety of clinical trials, the US Food and Drug Administration (USFDA) conducts inspections to evaluate compliance with established regulations. Aims: To examine the USFDA's inspections and non-compliance actions taken against clinical research organizations (CROs) over a 13 years period. Methods: The study utilizes a comprehensive dataset compiled from publicly available records, including inspection reports, warning letters, and other regulatory documents issued by the USFDA. Through systematic data collection and analysis, this study seeks to shed light on the frequency and nature of non-compliance findings, identify common areas of concern, and evaluate the effectiveness of regulatory actions. Results: The study reveals patterns and trends in the USFDA's inspections, highlighting key compliance challenges faced by CROs. These challenges include issues related to study protocols, informed consent, data integrity, adverse event reporting, and adherence to good clinical practice (GCP) guidelines. Furthermore, this analysis explores the USFDA's warning letters to assess their impact on CROs' compliance efforts. Conclusions: The findings of this retrospective analysis can inform CROs, and other stakeholders about the areas of greatest concern in clinical research compliance. The study contributes to the ongoing efforts to enhance the quality and integrity of clinical trials, ultimately benefiting patient safety and the credibility of the research enterprise.

Phase IV Studies: What Clinicians Need to Know!

Phase IV trials, also known as postmarketing safety and efficacy studies and postmarketing surveillance (PMS) studies, occur after a drug or medical device has received regulatory approval and is available in the market. These trials are designed to collect additional information regarding the product's safety, efficacy, and prolonged effects in a larger and more diverse patient population. The foremost goal of phase IV trials is to detect any rare or long-term adverse effects that may not have been identified during the prior phases of clinical development. During phase IV trials, pharmaceutical companies, academic institutions, or other research organizations conduct studies to evaluate various aspects of the product, including its real-world effectiveness, optimal use, and any potential safety concerns. The regulatory agencies play a role in overseeing these trials to ensure that they are conducted ethically and in compliance with good clinical practice (GCP) guidelines.

Randomised controlled trial on the effect of social support on disease control, mental health and health-related quality of life in people with diabetes from Côte d’Ivoire: the SoDDiCo study protocol

IntroductionDiabetes mellitus (DM) and its severe complications contribute significantly to disability and, hence, burden of disease. Poor mental health, a frequent DM consequence, may hinder successful diabetes control in low-income...

Microbiological Profile and Clinical Features of Septic Arthritis of the Shoulder: A 10-Year Cohort Single-Centre Study.

Introduction Septic arthritis (SA) constitutes a pressing orthopedic emergency characterized by acute, non-traumatic joint pain. Timely diagnosis and intervention are imperative to avert complications such as chondrolysis and systemic sepsis. The etiology is predominantly hematogenous, necessitating an integrated approach involving surgical and microbiological modalities. Shoulder aspiration and microbiological analysis play pivotal roles in guiding treatment, especially when positive findings prompt more aggressive therapeutic strategies. This study aims to elucidate the nuanced clinical and epidemiological characteristics of septic arthritis in both native and prosthetic joints within a singular institutional cohort over a decade. Methods This retrospective case series analysis spanned a 10-year period, focusing on non-prosthetic shoulder joints from January 2012 to July 2021. In this timeframe, only 183 aspirations were performed and sent to the microbiology department for analysis, including cultures, microscopy, and antibiotic sensitivity tests for positive cultures. The study delved into the microbiological profile of infections, encompassing gram stain, culture positivity rates, identification of microorganisms, and antibiotic susceptibility patterns. Additionally, the incidence of primary joint infections with resistant strains, particularly methicillin-resistant Staphylococcus aureus(MRSA), was scrutinized. Statistical analysis utilized the SPSS program version 20.0 (IBM Inc., Armonk, New York), with a significance level set at 5%. The project, registered with the trust's clinical audit department (Reg #5372), adhered to the Declaration of Helsinki and good clinical practice guidelines. Data collection involved extracting non-identifiable patient modifiers from the laboratory database bank into Excel spreadsheets. Results The study included 183 patients, with 108 (59%) females and 75 (41%) males. The average age was 76.2±16.5 years. Among them, 138 (75.4%) reported pain, and 15 (8.2%) had a body temperature over 37.8°C. Lab results showed a mean white blood cell count of 11.6±4.5 and an average C-reactive protein level of 121.7±102.1. Leucocytosis (>11,000 WBC) was seen in 82 (44.8%) cases. Elevated C-reactive protein (CRP; >10 mg/dl) was found in 136 (74.3%) patients. Synovial fluid analysis revealed no crystals in 91.3% of cases. Microbial resistance analysis showed 19 strains resistant to co-trimoxazole and 11 to erythromycin. Among co-trimoxazole-resistant strains, 73.7% were Staphylococcus aureus, a statistically significant association (p<0.001). Conclusion The evolving sensitivity patterns of microbes in septic arthritis underscore the necessity to reassess empirical antibiotic therapy. Subsequent joint damage resulting from infection can result in substantial disability.

Oncology Early-Phase Clinical Trials in the Middle East and North Africa: A Review of the Current Status, Challenges, Opportunities, and Future Directions

ABSTRACT Clinical trials, the empirical discipline of medical experimentation conducted on human subjects, have engendered a paradigm shift in medical research. The need for new clinical studies is paramount in the Middle East and North Africa (MENA) region, with its rising cancer incidence and demand for efficient oncology treatments. This paper comprehensively reviews the challenges, opportunities, and future directions of phase I oncology clinical trials in the MENA region. Early-phase trials are vital in determining drug dosage and assessing toxicity, bridging the gap between preclinical research and clinical practice. Considering the unique landscape of MENA, this review explores regulatory aspects, specific hurdles faced, potential advantages, and areas for improvement in conducting these trials. Various future directions can be pursued to maximize the potential of phase I oncology trials in MENA. While regulatory bodies like the Ministry of Health adhere to the International Conference on Harmonization–Good Clinical Practice guidelines, a unified system meeting high standards would yield better results. Strengthening research infrastructure, establishing research centers, incorporating clinical trial education into the curriculum, and improving access to medical facilities are crucial. Enhancing consumer understanding of research would facilitate increased participation and promote sustainability in trial recruitment. Navigating various funding sources would open the door for more funding opportunities. Collaborations between academia, industry, and regulatory bodies, both international and local, should be fostered to promote knowledge sharing, resource pooling, and harmonization of standards. Such collaborations would contribute to the sustainability of clinical trial activities by leveraging collective expertise, sharing research infrastructure, and distributing the burden of regulatory compliance. By adopting these strategies, the MENA region can advance its capacity to conduct early phases of oncology trials and contribute significantly to the global medical research landscape.

A Review on CDSCO: Central Drug Standard Control Organisation

India has been a hub for managing various multi centre trials the central drug standard control organisation (CDSCO), headed by the drug controller general of India (DCGI), drowsing the regulation for the manage of clinical trials in India the conduct of trails, regulations in India and quality of data generated may be the source for this evolution it is crucial that now all clinical trials conducted in India should as per the international conference of harmonization good clinical practice guidelines ( ICH- GCP) for clinical trials and follow the newly amended schedule Y of the drugs and cosmetic Act.

Protocol for the Tallaght University Hospital Institute for Memory and Cognition-Biobank for Research in Ageing and Neurodegeneration

IntroductionAlzheimer’s disease and other dementias affect >50 million individuals globally and are characterised by broad clinical and biological heterogeneity. Cohort and biobank studies have played a critical role in advancing...

간호대학생을 위한 팀프로젝트기반 임상시험연구 교육의 효과

Objectives Project-based learning engages students in practical activities related to course contents and has been demonstrated to improve academic performance. Nurses play a particularly important role in promoting clinical trial research as a new professional workforce. An entry-leveled educational course was developed to learn the future professional workforce roles in clinical trial research for nursing students. This study evaluated the effectiveness of a clinical trial research course on the importance and performance of the clinical research coordinators' role, students' recognized achievement, and cooperative self-efficacy.&#x0D; Methods Five professional clinical coordinators and two nursing professors developed the four projects on the clinical research processes and roles based on Good Clinical Practice guidelines. Thirteen junior students divided into 4 small groups completed a new project-based clinical research course composed of 8 sessions of clinical field work, discussion, reflection, portfolio, and presentation from September to October 2022. Students responded questionnaires on the importance-performance clinical trial nurses' roles, recognized achievement, and cooperative self-efficacy, and reported the reflective journal on the class. The students' class evaluation data was retrieved and analyzed using importance-performance analysis (IPA) and Wilcoxon signed rank test.&#x0D; Results Compared to baseline scores, protocol assessment (z=-2.59, p=.010), protocol planning (z=-1.96, p=.050), and subject recruitment (z=-2.16, p=.031) increased among the 8-section of clinical trial coordinator's roles. Additionally professional role recognition increased after the class (z=-2.25, p=.025). IPA analysis exhibited that nursing students recognized the 8-section clinical trial nurses' roles as more important and more performing. The mean score of nursing students' recognized achievement was high (4.96 points out of 5 points), and cooperative self-efficacy was high (4.37 points out of 5 points) after completing a clinical trial research course.&#x0D; Conclusions An entry-leveled educational course on the clinical trial research using project-based learning may expand the possibility of a new professional career for nursing students.

Needle-tip electrocautery versus steel scalpel incision in neurosurgery: study protocol for a prospective single-centre randomised controlled double-blind trial

IntroductionElectrocautery is used widely in surgical procedures, but making skin incision has routinely been performed with scalpel rather than electrocautery, for fear that electrocautery may cause poor incision healing, excessive...