Clinical Research Methodology Research Articles

Redesigning a Stopped Clinical Trial as an Emulated Trial Using Real-World Data to Explore the Effectiveness of Slow-Release Oral Morphine as a Treatment for Opioid Use Disorder.

Canada is currently experiencing a problematic opioid crisis with increasing mortality rates. Traditional randomized controlled trials (RCTs) that examine the effectiveness of pharmacological treatment options for people with opioid use disorder (OUD) are challenging to conduct. An increasingly popular methodology is through the implementation of emulated clinical trials, a methodology in which key elements of a "target" RCT are replicated using previously collected healthcare-based data. They can possibly address some of the common challenges found in the conduct of RCTs, such as prolonged timelines, high cost, and poor participant recruitment. In effect, emulated trials accelerate knowledge generation by producing real-world evidence that can be akin to phase 3 effectiveness trials, without any need to recruit live participants or administer investigational products. During the COVID-19 pandemic, several trials were stopped due to increased pandemic-related research restrictions, leaving important questions about OUD treatment unanswered. In this commentary, we describe the transition of a traditional RCT to an emulated trial spurred by challenges posed by the COVID-19 pandemic. We describe our transition using a notable published framework with regards to the population sample, interventions, outcomes, and proposed analyses. This commentary aims to help other researchers and trialists apply emulated trials in substance use research and beyond, emphasizing the role of this methodology in clinical research and advancing scientific knowledge that could be otherwise lost or unattainable.

Virtual Education is the Need of the Hour for the Global Gastroenterology Community: A Survey of Leaders of Professional Gastroenterology Organizations.

Since the onset of the Coronavirus disease 2019 (COVID-19) pandemic, there has been a significant opportunity to leverage virtual platforms for communication and dissemination of knowledge. An online survey was conducted to examine the viewpoints of World Gastroenterology Organization (WGO) leaders concerning the necessity, primary priority areas, and implementation strategies for a virtual global gastroenterology educational program. We conducted a survey of leaders of WGO member societies to assess their opinions on creating opportunities for global education using virtual platforms, identifying practical implementation steps and priority educational areas. Responses were obtained from 57/117 (48.7%) contacted leaders with 56/57 (98.2%) identifying such a need. Five mutually exclusive priority educational topics were proposed in the survey: clinical gastroenterology, endoscopy, nutritional support, research methodology, and professional development. Overall, most participants prioritized clinical gastroenterology (45/57; 78.9%) and endoscopy/hand skills (27/57; 47.3%) as educational topics to be addressed by the virtual global gastroenterology educational program. A majority of WGO member society leaders surveyed favored monthly teaching activities (33/57; 57.8%), ideally carried out between 1500-2100 local time (31/57; 54.3%), ideally with no administrative fees (47/57; 82.4%). This truly global survey of WGO member societies achieved a good response rate and provides important insights into the need for and scope of future virtual education programs under the aegis of the WGO.

The role of standardized quality systems in the management of a healthcare provider

Review Article, Pol J Public Health, Vol. 134 (2024): 69-72 Daria Żuraw, Paulina Oleksa, Mateusz Sobczyk, Kacper Jasiński, Mikołaj Porzak, Alicja Sodolska, Monika Żybowska, Anna Rzewuska-Fijałkowska Student Scientific Association at the Chair and Department of Epidemiology and Clinical Research Methodology, Medical University of Lublin, Poland DOI_disc_logo 10.12923/2083-4829/2024-0015 © 2024 Author(s). This is an open access article distributed under the Creative Commons Attribution-NonComercial-No Derivs licence (http://creativecommons.org/licenses/by-nc-nd/3.0/) Abstract Since the 1940s, the healthcare sector in Poland has been in constant evolution and requires constant improvement in the quality of services provided and customer-patient satisfaction. To facilitate quality management, systems dedicated to healthcare entities have been developed over the years, and others have been adapted to medical facilities. These methods are based on efficient, planned, repeatable, documented procedures based on current medical knowledge. The key is to choose the right system, tailored to the way the entity operates. A quality management system defines: organizational structure, available resources, procedures and processes to be implemented, the way information and documents communicate and flow, and the responsibility for quality assurance care and compliance. Creating awareness and a pro-quality attitude in the field of medical services makes it possible to learn about instruments and solutions aimed directly at healthcare provider, as well as those that can be adapted and subsequently implemented. Keywords: ISO standards, accreditation standards, total quality management, adverse events, medical mistake, management.

Metformin – the old drug with new therapeutic possibilities

Original Article, Pol J Public Health, Vol. 134 (2024): 47-51 Paulina Oleksa, Kacper Jasiński, Daria Żuraw, Mateusz Sobczyk, Monika Żybowska, Anna Rzewuska-Fijałkowska, Karolina Haczkur-Pawłowska, Piotr Więsyk Students’ Scientific Society at the Department of Epidemiology and Clinical Research Methodology, Medical University of Lublin, Poland Introduction. Metformin is an oral antidiabetic drug from the biguanide group, popularly referred as an aspirin of the 21st century. The therapeutic targets of metformin are expanding. It is characterized by antineoplastic, immunoregulatory, anti-aging and neuroprotective properties. We aimed to evaluate the pleiotropic effects of metformin, taking into account its different mechanisms, efficacy and safety in contemporary public health challenges. Material and methods. We conducted the literature review from 2014 to 2024 using the PubMed and Google Scholar. Results. Metformin, depending on the cancer and its stage, enhances the cancer treatment effects, prevents the drug resistance, lengthens overall time of survival, reduces the risk of recurrence. In the Parkinson’s disease, Alzheimer’s disease and depression metformin can even increase the risk of their occurrence, especially in high doses. Such doses predispose to the cobalamin deficiency, affecting the functioning of the nervous system. Metformin was effective in seizure control of epilepsy. It has positive impact on the course of some autoimmunological diseases. Among diabetics treatment, outcomes of COVID-19 and tuberculosis could be improved by metformin. Conclusions. Metformin is pluripotential drug. Possibilities of adjuvant metformin therapy are very promising, but it cannot be recommended as standard treatment. This issue requires further investigation, preferentially randomized controlled trials on the bigger research samples. Keywords: metformin and therapy, metformin and treatment, metformin and advances.

The Role of Clinical Research in Improving Medical Practice: From Theory to Practice

Clinical studies can be relied on as a powerful engine of medical advancement in terms of developing new solutions for better life treatment. This paper reviews research approaches that are critical for the establishment of the safety and efficacy of various treatment methods. Even though research is becoming more advanced day by day, still a gap exists between the research findings and their real application. The purpose of this review is to identify barriers that stand in the way of translation and to provide means for overcoming them. A comprehensive search of online databases identified studies on clinical research methodologies and evidence-based practice (EBP) promotion. Thematic analysis was used to synthesize key themes. This paper demonstrates how clinical research particularly matters. It denotes problems like expenses limits as well as clinicians’ unawareness that do not allow the translation of research results into practice. Nevertheless, efforts are made to provide solutions, including education on EBP, adoption of practice guidelines and leveraging technology to share research findings. These problems should be tackled by EBP promotion in order to guarantee optimum and updated treatment of patients and better population health.

A Systematic Review of Reported Outcomes in Randomized Controlled Trials Targeting Early Interventions in Moderate-to-Severe Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Randomized controlled trials (RCTs) are the cornerstone to evaluate the efficacy of an intervention. To assess the methodology of clinical research, we performed a systematic review that evaluated the different outcomes used in RCTs targeting the early phase of moderate-to-severe adult TBI from 1983 to October 31, 2023. We extracted each outcome and organized them according to the COMET and OMERACT framework (core area, broad domains, target domains, and finally outcomes). A total of 190 RCTs were included, including 52,010 participants. A total of 557 outcomes were reported and classified between the following core areas: pathophysiological manifestations [169 RCTs (88.9%)], life impact [117 RCTs (61.6%)], death [94 RCTs (49.5%)], resource use [72 RCTs (37.9%)], and adverse events [41 RCTs (21.6%)]. We identified 29 broad domains and 89 target domains. Among target domains, physical functioning [111 (58.4%)], mortality [94 (49.5%)], intracranial pressure target domain [68 (35.8%)], and hemodynamics [53 (27.9%)] were the most frequent. Outcomes were mostly clinician-reported [177 (93.2%)], while patient-reported outcomes were rarely reported [11 (5.8%)]. In our review, there was significant heterogeneity in the choice of end-points in TBI clinical research. There is an urgent need for consensus and homogeneity to improve the quality of clinical research in this area.

Trainee tips for conducting a clinical trial during the Clinical Psychology Doctorate

The research component of doctoral training in clinical psychology can evoke a range of emotions, from excitement to apprehension, often influenced by prior experience and the nature of the research undertaken. This article shares reflections on conducting a feasibility randomised controlled trial (RCT) as part of a clinical psychology thesis, offering practical advice to ease the process for trainee clinical psychologists considering a clinical trial for their doctoral research. Key insights include the importance of selecting experienced supervisors, starting early, deciding between a feasibility or full-scale trial, determining recruitment sources, staying organised, building positive relationships with researchers and participants, and choosing a topic of genuine interest. Conducting a clinical trial during clinical psychology training, despite its challenges, can provide invaluable experience and skills, fostering a deeper understanding of clinical research methodologies and their practical applications.

Semi-automated software improves interrater reliability and reduces processing time of magnetic resonance imaging-based exocrine pancreatic assessments in pediatric patients

ObjectivesMagnetic resonance (MR) imaging with secretin stimulation (MR-PFTs) is a non-invasive test for pancreatic exocrine function based on assessing the volume of secreted bowel fluid in vivo. Adoption of this methodology in clinical care and research is largely limited to qualitative assessment of secretion as current methods for secretory response quantification require manual thresholding and segmentation of MR images, which can be time-consuming and prone to interrater variability. We describe novel software (PFTquant) that preprocesses and thresholds MR images, performs heuristic detection of non-bowel fluid objects, and provides the user with intuitive semi-automated tools to segment and quantify bowel fluid in a fast and robust manner. We evaluate the performance of this software on a retrospective set of clinical MRIs.MethodsTwenty MRIs performed in children (< 18 years) were processed independently by two observers using a manual technique and using PFTquant. Interrater agreement in measured secreted fluid volume was compared using intraclass correlation coefficients, Bland-Altman difference analysis, and Dice similarity coefficients.ResultsInterrater reliability of measured bowel fluid secretion using PFTquant was 0.90 (0.76–0.96 95% C.I.) with − 4.5 mL mean difference (-39.4–30.4 mL 95% limits of agreement) compared to 0.69 (0.36–0.86 95% C.I.) with − 0.9 mL mean difference (-77.3–75.5 mL 95% limits of agreement) for manual processing. Dice similarity coefficients were better using PFTquant (0.88 +/- 0.06) compared to manual processing (0.85 +/- 0.10) but not significantly (p = 0.11). Time to process was significantly (p < 0.001) faster using PFTquant (412 +/- 177 s) compared to manual processing (645 +/- 305 s).ConclusionNovel software provides fast, reliable quantification of secreted fluid volume in children undergoing MR-PFTs. Use of the novel software could facilitate wider adoption of quantitative MR-PFTs in clinical care and research.

Development of a topic‐specific bibliographic database supporting the updates of SPIRIT 2013 and CONSORT 2010

AbstractIntroductionAn important mechanism of research waste is inadequate incorporation of, and references to, previous relevant research. Identifying references for a research manuscript can be challenging, in part due to the exponential rise in potentially relevant literature to consider. For large research projects, such as developing or updating reporting guidelines, it may be helpful to construct a supportive topic‐specific bibliographic database.MethodsIn support of updating the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 and the CONsolidated Standards Of Reporting Trials (CONSORT) 2010, we developed the SPIRIT‐CONSORT Evidence Bibliographic database (SCEBdb): a freely available topic‐specific bibliographic database of publications providing an evidence foundation for the updates. We searched multiple sources of potential publications and tagged included ones with database‐specific keywords. For context, we also formulated 10 core considerations for constructing topic‐specific bibliographic databases and identified and described 5 illustrative other databases.ResultsAs of April 2024, the SCEBdb included 846 publications. The database proved useful as a supplementary information source for our scoping review of published comments on SPIRIT 2013 and CONSORT 2010, for a supplementary Delphi process, and in the writing phase of the guidance documents. We expect that the database will be useful for future projects within the fields of clinical research methodology, bias, evidence synthesis, and randomized trials.ConclusionThe methods involved in constructing the SCEBdb, and our suggested core considerations for topic‐specific bibliographic databases, could be helpful for researchers reflecting on whether, and how, to develop a topic‐specific bibliographic database.

Clinical Research Methodologies: Choosing the right approach for successful trials

Clinical Research Methodologies: Choosing the right approach for successful trials

Using digital tools in clinical, health and social care research: a mixed-methods study of UK stakeholders

ObjectiveThe COVID-19 pandemic accelerated changes to clinical research methodology, with clinical studies being carried out via online/remote means. This mixed-methods study aimed to identify which digital tools are currently used...

Clinical research methodology: A narrative review

Research necessitates a systematic approach, meticulous planning, and execution as planned. The study consists of predefined components, such as aims, population, conduct/technique, outcome, and statistical considerations. Understanding the fundamental aspects of methodology is crucial for any researcher, as it ensures objective, reliable, and repeatable results. This narrative review explored various aspects of the methodology used in conducting clinical research. A literature search was conducted using relevant keywords from various databases and article bibliographies.

Analysis of clinical research features and outcome indexes of traditional Chinese medicine intervention in septic kidney injury

This study aims to systematically review the clinical features and outcome indicators in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) intervention in septic kidney injury and provide a reference for optimizing clinical study design and building the core outcome set(COS) of TCM treatment of septic kidney injury. Computer searches were conducted on PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed to find published RCT of TCM intervention in septic kidney injury in the past five years, extract the basic characteristics, intervention measures, outcome indicators, and other data of included studies, and conduct descriptive analysis. 53 RCTs were included, and the sample size was mostly concentrated in 60-80 cases, with abdominal infection being the most common(15 articles, 83.3%) and the TCM syndrome of blood stasis being the most frequent(9 articles, 50.0%). The frequency of intervention methods from high to low were TCM decoction(28 articles, 52.8%), Chinese patent medicine(22 articles, 41.5%), and combined TCM therapy(3 articles, 7.5%); the intervention time of the trial was more than 7 d(34 articles, 69.4%). The risk of bias in included studies was unclear. A total of 84 outcome indicators were involved, which were divided into 9 fields, including 63 physical and chemical tests(305 times, 72.2%), 4 kinds of disease degree(48 times, 11.6%), 4 kinds of clinical effective rate(15 times, 3.6%), 1 kind of quality of life(1 time, 0.2%), 2 kinds of economic evaluation(14 times, 3.3%), 1 kind of TCM disease(9 times, 2.1%), 2 kinds of long-term prognosis(16 times, 3.8%), 2 kinds of safety events(6 times, 1.4%), and 5 other indicators(8 times, 0.7%). The cumulative frequency was 422 times, among which the outcome indicators with higher frequency were inflammatory factors(42 articles, 79.2%) and markers of renal function and kidney injury(40 articles, 75.5%). Only 1(1.9%) of the included articles mentioned primary and secondary outcome indicators, and 6 articles(11.3%) mentioned safety events, 13 articles(24.5%) mentioned economic assessment. The RCT quality of TCM intervention in septic renal injury was generally low, and the reference standards for sepsis, kidney injury, and TCM syndrome diagnosis were not uniform. There are some problems in outcome indicators, such as unclear distinction between primary and secondary indicators, neglect of endpoint indicators, lack of application of TCM characteristic indicators, and insufficient attention to safety events and economic assessment. It is suggested that the quality of clinical research methodology should be improved in the future, and the COS should be constructed to provide high-level evidence-based evidence for TCM intervention in septic kidney injury.

A Serious Shortfall in Clinical Research in Doctoral Schools: A Detailed Analysis of Ten Doctoral Schools of Medicine

The amount and quality of clinical research are constantly increasing; however, the translation of results into daily practice is not keeping pace. University curricula provide minimal methodological background for understanding the latest scientific findings. In this project, we aimed to investigate the quality and amount of clinical research compared with basic research by analysing ten doctoral schools in Hungary. We found that 71% of PhD theses were submitted in basic sciences. The majority of physicians (53%) working in clinical institutions did their PhD projects in theoretical departments. Importantly, recent clinical methodologies such as pre-registered randomized clinical trials and meta-analysis are only rarely used (1% and 1%, respectively) compared with retrospective data analysis or cross-sectional studies (30% and 43%, respectively). Quality measures such as international registration, sample size calculation, and multicentricity of clinical sciences are generally absent from articles. Our results suggest that doctoral schools are seriously lagging behind in both teaching and scholarly activity in terms of recent clinical research methodology. Innovation and new educational platforms are essential to improve the proportion of science-oriented physicians.

A hybrid spatiotemporal deep belief network and sparse representation-based framework reveals multilevel core functional components in decoding multitask fMRI signals.

Decoding human brain activity on various task-based functional brain imaging data is of great significance for uncovering the functioning mechanism of the human mind. Currently, most feature extraction model-based methods for brain state decoding are shallow machine learning models, which may struggle to capture complex and precise spatiotemporal patterns of brain activity from the highly noisy fMRI raw data. Moreover, although decoding models based on deep learning methods benefit from their multilayer structure that could extract spatiotemporal features at multiscale, the relatively large populations of fMRI datasets are indispensable, and the explainability of their results is elusive. To address the above problems, we proposed a computational framework based on hybrid spatiotemporal deep belief network and sparse representations to differentiate multitask fMRI (tfMRI) signals. Using a relatively small cohort of tfMRI data as a test bed, our framework can achieve an average classification accuracy of 97.86% and define the multilevel temporal and spatial patterns of multiple cognitive tasks. Intriguingly, our model can characterize the key components for differentiating the multitask fMRI signals. Overall, the proposed framework can identify the interpretable and discriminative fMRI composition patterns at multiple scales, offering an effective methodology for basic neuroscience and clinical research with relatively small cohorts.

Development and validation of a sensitive UPLC-MS/MS analytical method for GFH009 in rat plasma and its application to toxicokinetics studies.

GFH009 is a potent, highly selective, small molecule that targets and inhibits the activity of the CDK9/cyclin T1 regulatory complex of P-TEFb. This study aimed to develop and validate a highly selective and sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for precise quantification of GFH009 in rat plasma. This method was subsequently employed for conducting toxicokinetic studies of GFH009 in rats. Plasma was prepared using a simple protein precipitation method by acetonitrile. Chromatographic separation of the analytes was achieved on a BEH C18 analytical column with a rapid 3.0 min run time and a flow rate of 0.5ml/min. The calibration curves for plasma samples exhibited excellent linearity over a wide concentration range of 1.0-1,000 ng/ml for GFH009. Intra- and inter-day accuracies were within 92.7-105.7%, and precisions were no more than 6.7%. Furthermore, the analyte demonstrated stability under four different storage conditions, with variations of <15.0%. This study pioneers a methodological innovation by introducing a highly reliable, specific and sensitive analytical method for GFH009 in rat plasma. The successful application of this method in toxicokinetic studies further underscores its significance, offering valuable insights for the methodology of clinical pharmacokinetic research.

Knowledge, Attitude, and Practice of Medical Students About Medical Research in Mansoura University, Egypt

Abstract&#x0D; Objectives: Medical students are the bright future researchers and giving priority to their early research experiences will have its remarkable effect on research evolution. Recent advances in medical fields are challenging and increase the importance of attracting new researchers. This study describes knowledge, attitude, practice, and barriers to participation in research among undergraduate medical students. &#x0D; Methods: This is a cross-section study on 260 medical students. Data collected included: knowledge about research (nine multiple questions); attitude towards medical research (eight questions); practice of research (five questions) and barriers against participation in research (nine questions).&#x0D; Results: Some aspects of research knowledge were affected by students’ sex, previous year grade, academic phase, and premedical school type. About 44.6% gave right answers about parts of scientific papers. Academic phase medical students had better research knowledge than clinical phase students. More than 80% of study participants agree on the importance of being oriented about clinical research methodology. Lack of time was the most addressed barrier against participation in research projects by the students (50.5% of clinical phase students). &#x0D; Conclusions: Raising students’ awareness about the importance of research, improving students’ attitude, and removing barriers could improve their participation and experience in research.

Clinical Research in Prehospital Care: Current and Future Challenges.

Prehospital care plays a critical role in improving patient outcomes, particularly in cases of time-sensitive emergencies such as trauma, cardiac failure, stroke, bleeding, breathing difficulties, systemic infections, etc. In recent years, there has been a growing interest in clinical research in prehospital care, and several challenges and opportunities have emerged. There is an urgent need to adapt clinical research methodology to a context of prehospital care. At the same time, there are many barriers in prehospital research due to the complex context, posing unique challenges for research, development, and evaluation. Among these, this review allows the highlighting of limited resources and infrastructure, ethical and regulatory considerations, time constraints, privacy, safety concerns, data collection and analysis, selection of a homogeneous study group, etc. The analysis of the literature also highlights solutions such as strong collaboration between emergency medical services (EMS) and hospital care, use of (mobile) health technologies and artificial intelligence, use of standardized protocols and guidelines, etc. Overall, the purpose of this narrative review is to examine the current state of clinical research in prehospital care and identify gaps in knowledge, including the challenges and opportunities for future research.

Evidence-based medicine: new in the search for evidence

The review is focused on discussing new trends in DM, rethinking the evidence base medicine with an emphasis on demonstrating the efficacy and safety of new therapeutic agents and medical technologies, from gene editing to AI algorithms. At the same time, clinical trials of drugs are also not standing still, there is active development, new approaches, methods and designs are being developed. The process of drug development, registration and market launch of any drug takes a significant period of time, requires high financial costs and human resources. The gold standard of evidence-based medicine was initially considered to be RCTs, but at the same time, they have objective disadvantages: limited sample, inability to control all factors; insufficient follow-up time,negative impact on participants, inability to determine cause-and-effect relationships; limited measurement methods, limited budget and others. This review discusses the trends in the methodology of clinical research. The active implementation of new designs such as Adaptive Clinical Trials, "Master" protocols including Umbrella Study, Basket Study, Platform Studies, Master Observational Trials and the increased use of Single Patient Trials (N-of-1 trials) are allowing studies to become more efficient, relevant and applicable to real-life health care practice settings and patient-centered. In the review, we also look at both the pros and cons of the expanded use of biomarkers and Digital Endpoints in clinical trials and virtual clinical trials, which use mathematical models to study patient heterogeneity and its impact on various therapeutic questions. The process of expertise and regulatory approval continues to slow down the entry of drugs into the pharmaceutical market. The review considers changes in the approaches of regulators (FDA, EMEA and Russian Ministry of Health) to the drug registration procedure. The COVID-19 pandemic and sanctions have led to the need to expand the list of drugs with authorized accelerated registration. However, accelerated registration raises many questions regarding the sufficiency of the level of evidence and safety. As we can see a deep synthesis and integration of all available data is needed to achieve the next generation of evidence-based medicine. The major challenge in the next two decades will be to exploit the potential of multidimensional evidence generation by extracting, collating and generating large data sets of natural course of disease, genomics and all other omics analyses, all published clinical trials, RWD to provide next generation evidence.

Improving the Teaching of Histology by Using the Manual Whole Slide Imaging Technology

The tissue sample analysis based on the visualization of the entire tissue sample represents an important methodology in clinical diagnostics, research, and education. This process that enables visualization of the entire tissue sample is named whole slide imaging. For clinical purposes, professional and very expensive scanners are used for tissue sample digitization and the creation of whole slide images. In education, it is possible to use whole slide images that do not necessarily follow strict medical standards and regulations. Therefore, the important research task is to propose a methodology for the manual creation of whole slide images and its adequate use in medical education. In this paper, the use of manually created whole slide images in histology classes education was analyzed. In the experimental part of this research, the methodology of manual creation and usage of whole slide images (WSI) in histology education is presented in more detail. The subjective assessment of the user's satisfaction with WSI usage in education was also performed. It was shown that the whole slide images were evaluated very positively in the histological analysis and education process. Using WSI can significantly improve histology teaching, especially when distance education principles are implemented. Therefore, in crises like the pandemic situation COVID-19 WSI usage becomes a very important educational tool for teaching microscope-related topics. The results of this research showed that the use of whole slide images in histology classes is in line with the process of digital transformation in education.