Stages Of Trials Research Articles

Peptide and m-RNA Vaccines: Peculiarities of Immunogenicity and Protective Effect

Relevance. Pandemic pathogen variants formation is a pressing issue of modern healthcare system thus classic approaches of preventive measures against infectious diseases require revision including implementation of effective, safe, universal and rapid methods of vaccine production.Aim. To conduct analysis of scientific literature concerning peculiarities of m-RNA and peptide vaccines. Search of publications was carried out in PubMed, Google Scholar and e-library databases.Conclusions. In addition to obvious advantages both vaccine platforms have disadvantages. m-RNA vaccines are thermally unstable and need to be stored and transported at temperature not exceeding minus 80 °C which significantly reduces their availability in countries with low income. m-RNA vaccine platform was chosen to manufacture vaccines against SARS-CoV-2 in Western countries (USA and Germany) during the COVID-19 pandemic despite the mentioned disadvantage. Most perspective mRNA vaccine prototypes vaccine were designed to combat influenza, respiratory syncytial virus, rabies, malaria, HIV, Ebola virus, Zika virus and cytomegalovirus. Peptide vaccines are undemanding to external factors such as temperature of storage and transportation. On the other hand, they need to be more immunogenic which is achieved by adding various adjuvants. They are also challenging to manufacture due complexity of quaternary structure of protein epitopes of antigens. To date, foreign peptide vaccines against influenza, HIV infection, hepatitis C, tuberculosis, malaria, and leishmaniasis have passed the first and second stages of clinical trials. Both mRNA and peptide vaccines undergo rapid degradation in human body, which prompts scientists to develop new molecular methods for delivering the vaccine matrix to target cells

Flanking Effect on the Folding of Telomeric DNA Sequences into G-Quadruplex Induced by Antimalarial Drugs.

The folding of the guanine repetitive region in the telomere unit into G-quadruplex (G4) by drugs has been suggested as an alternative approach for cancer therapy. Hydroxychloroquine (HCQ) and chloroquine (CQ) are two important drugs in the trial stage for cancer. Both drugs can induce the folding of telomere-guanine-rich sequences into G4 even in the absence of salt. However, the guanine repetitive telomeric sequences are always flanked by other nucleobases at both the terminal (5' or 3') that can affect the drug-induced folding pathways and stability of the G4 significantly. Hence, in this study, the HCQ and CQ drug-induced folding of the guanine repetitive telomeric sequences into G4 and its stability by varying the chemical nature, number, and positions of the flanking nucleobases has been explored using several biophysical techniques and docking studies. It has been found that the drug-induced folding of telomere with single flanking nucleobases is similar to that without flanking nucleobases irrespective of the chemical nature and position of the flanking nucleobase. However, the propensity of the folding and the stability of the telomeric G4 induced by drugs decrease significantly with the increase of the flanking nucleobases more than one of any chemical nature and position. The data suggest that the number of flanking nucleobases rather than their chemical nature and location is a critical factor in the folding of the telomere into G4 induced by both drugs. Further, it has been observed that both drugs mainly interact with the G-tract and thymine of the loop region rather than the flanking nucleobases of the telomeric sequences without or with one flanking nucleobase. In contrast, the flanking nucleobases also participate in the interaction with the HCQ and CQ along with the core guanine repeat telomeric unit in the case of the telomeric sequences with more than one flanking nucleobases. The participation of the flanking nucleobases in the interaction with the HCQ and CQ affects the hydrogen bonding of the positively charged side chain of drugs with G quartet and loop nucleobases of telomere along with the with π···π and C-H···π weak interactions between the quinoline part of the drugs with the core telomeric guanine repeat unit which affects the folding pattern of the telomere sequences with more than one flanking nucleobases into G4.

Potential of mRNA therapy in the treatment of cardiovascular diseases

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alarmed the global community due to the significant loss of human lives during the pandemic. However, as the saying goes, every cloud has a silver lining. A positive aspect of this recent pandemic has been that it stimulated scientists to create vaccines against SARS-CoV-2, accelerating the emergence of new therapeutic agents based on messenger ribonucleic acid (mRNA). Numerous mRNA therapeutic products are currently in development, with dozens at various clinical trial stages. These products have facilitated significant changes in the paradigm of medical therapy, including the treatment of cardiovascular diseases (CVD). Although most of these cardiovascular mRNA therapeutics are still in preclinical development, phase IIa trials for myocardial ischemia therapy have already been completed with encouraging results. The scope of mRNA therapy for CVD is extremely broad, potentially even limitless, with ongoing research including conditions like myocardial ischemia, heart failure, arrhythmias, hypercholesterolemia, and occlusive arterial diseases. Moreover, mRNA can be used to enhance the effectiveness of cell therapies. In the future, researchers predict that mRNA therapies will not only replace some existing biopharmaceuticals and pharmacotherapy methods but also be applied to treat previously considered untreatable cardiovascular diseases.

Characterization of medical device randomized controlled trials with adaptive designs.

Aim: Adaptive designs are frequently used in drug randomized controlled trials (RCTs). However, their use in medical device RCTs remains unclear. We aimed to characterize medical device RCTs with adaptive designs. Materials & methods: We searched for adaptive RCTs in the following databases: ClinicalTrials.gov, International Clinical Trials Registry Platform and the International Standard Randomised Controlled Trial Number registry. Adaptive design keywords and medical device corporation names were used as terms to search the trial records registered between 1 January 2000 and 18 October 2024 in the databases. The annual number and proportions of adaptive trials were analyzed, and characteristics such as design type, sponsor, therapeutic area, trial stage and regulatory status were summarized. Results: Overall, 105 adaptive RCTs were identified from ClinicalTrials.gov, accounting for 2.112 per 1000 trials in 49,721 medical device clinical trials registered in ClinicalTrials.gov during the period. The average annual number of adaptive RCTs per 1000 clinical trials was the highest (8.55±11.65) during 2005-2010, reduced to 3.33±2.35 during 2011-2016, and significantly decreased to 1.29±0.85 during 2017-2024 (p = 0.011). The most common adaptive designs were group sequential design (GSD, 50.5%), sample size reassessment (SSR, 17.1%) and investigating both superiority and non-inferiority (10.5%). Most RCTs were sponsored by the private sector (62.9%), conducted in Europe/North America (95.2%), in the field of heart disease (46.7%) and post-market trials (76.2%). Compared with pre-market RCTs, post-market RCTs showed more diverse adaptive designs such as response-adaptive randomization and adaptive enrichment. Conclusion: The average annual proportions of adaptive medical device RCTs in ClinicalTrials.gov has reduced in the last 10years. The most-used adaptive designs in medical device RCTs are GSD, SSR and investigating both superiority and non-inferiority.

NTRK translocation: from general to specific

The molecular-genetic profile of lung cancer is highly diverse, complicating the formation of a unified patient portrait and necessitating the incorporation of specific genetic testing into diagnosis. There are key mechanisms for the activation of oncogenes, including point mutations, copy number changes (amplifications), and fusions, which are observed in non-small cell lung cancer (NSCLC). Modern molecular-targeted therapy for patients with NSCLC increases the duration of disease control and, in some cases, can transform a once-fatal disease into a chronic condition. Currently, the standard testing panel includes the identification of mutations in the EGFR gene (exons 18–21), ALK translocations, ROS1 translocations, and BRAF V600E mutations. However, less common alterations such as RET and NTRK translocations also occur. The use of next-generation sequencing (NGS) allows for the identification of rarer genetic alterations. NTRK gene fusions are considered oncogenic factors for various solid tumors in both adults and children. The prevalence of NTRK gene alterations varies by tumor type. However, in lung cancer, this type of genetic alteration is rare, with an overall prevalence of less than 3%, and typically the occurrence rate is less than 1%. Currently, three drugs have been included in international clinical guidelines as potential treatment options for NTRK translocations, demonstrating their effectiveness. Several other drugs are at various stages of clinical trials. In this review, we will highlight the existing data for a better understanding of the patient profile with NTRK and present a clinical case.

Диагностика понимания драматического произведения младшими подростками: обоснование критериев

<p>The article discusses the problem of evaluating literary text understanding by teenagers aged 11–12. Theoretical analysis showed that the evaluation and development of dramatic text understanding is the most underestimated problem in pedagogical, philological, and psychological research. The diagnostic assessment «Understanding of Dramatic Texts» consists of two parts. The first part allows you to estimate the level of following reading skills: paratext interpretation; the ability to understand the emotional tone of the work; the ability to «recreate» the image of a literary hero; the ability to disclose the author’s claim. In this part of the study, the material used as the survey basis is presented by Alexander Vampilov’s dramatic work «Date» (1961). The second part of the discussed method is based on the creative transformation task. Aesop’s fable «The Liar» was used as epic text to be made into dramatic texts by the learners. The children’s works analysis allowed us to evaluate the formed within the study framework reading attitudes which are necessary for dramatic text decoding and understanding. We assessed the results in terms of form and content. The diagnostic assessment was conducted in three trial stages. First, we ran and recorded conversations with a reference group, which included 16 specialists in the field of philology and theater. This step allowed us to determine evaluation criteria. Grade 5–6 students took part in the second stage of testing. This stage made it possible to shorten and adapt the questionnaire for working with schoolchildren. In the third stage, the methodology was adapted for written implementation</p>

Sir Nicholas Gilbourne's (magical) cross-over trial of 1631.

We describe a basic 'cross-over' trial undertaken by Sir Nicholas Gilbourne of Kent, England, in or before 1631. This was used to test the effectiveness of 'weapon salve', an ointment claimed to cure 'sympathetically' (i.e. remotely) by application to the weapon that inflicted an injury. Gilbourne reports very basic outcomes but these represent key stages of a modern cross-over trial: no treatment, treatment, no treatment, treatment. We discuss the value of such historical vignettes - even a magical one - for medical students in two respects: understanding research methodology and learning about consultation strategies. Gilbourne's conclusion is clearly fanciful but the basic principles behind his experiment are sound. Historical examples like this can inspire medical students to think critically about research methods and treatment strategies.

The possibility of effective using the conservative and the minimally invasive treatment methods at various stages of the Dupuytren disease

A literature review is presented on the conservative and minimally invasive methods of treating the Dupuytren contracture. The investigators discuss both the methods implemented into clinical practice and those, which are currently at the stage of clinical and laboratory trials, including the minimally invasive methods, which can be used not only at the later stages, but also in cases of early manifestations of the disease. Among them there are the combined use of conservative methods, the radiation therapy, the injections of collagenase and steroids, the use of immunodepressive medicines and the needle aponeurotomy. These methods can be used at the earliest stages of the disease, however, the absence of proper evidence base often hinders their wide implementation. Up to the present moment, there is no commonly acknowledged approach to managing and treating the patients with early stage of the disease. The modern approach is focused on the invasive treatment of only later disease stages and of the severe contracture cases. This is why we would like to emphasize the potential of minimally invasive methods at the early stages of the Dupuytren disease, as well as the necessity of further research in this direction along with the importance of implementing such methods into everyday practice of the physicians.

Work-based learning design for students with disabilities in vocational high schools

Education for students with disabilities is urgently needed as part of fulfilling educational equality. This research is motivated by the lack of learning models that focus on students with disabilities, particularly Work-Based Learning for vocational high school students. The purpose of this research is to analyze the needs and develop a design for Work-Based Learning instructional tools for Vocational High School students with special needs. This research method uses the Borg and Gall model combined with the Dick and Carey instructional model, making the stages more contextual and providing a comprehensive overview. The subjects of this research are Vocational High School students from two provinces, namely Central Java and the Special Region of Yogyakarta, specifically students with special needs, including those with disabilities. The trial stages in this research start with evaluations by subject matter experts, media experts, and instructional design experts. The next step involves product testing, which includes individual trials, small-group trials, and large-group trials. The results are then analyzed descriptively and qualitatively to assess the developed model. Thus, based on these results, the model developed is in accordance with needs and has the potential to be implemented at the vocational school level as a means of facilitating WBL-based learning for students with special needs in Indonesia.

Analisis Yuridis Terhadap Permohonan Perwalian Dalam Pengurusan Izin Jual Tanah Anak Di Bawah Umur

In general, a child is someone who is not yet an adult or is not married. It is not possible for children under this age to carry out legal actions by themselves. For all legal actions, minors are under the authority of the Guardian. To sell land and buildings with the condition that parents act as guardians, you must apply for guardianship and apply for a permit to sell property for minors in the District Court. The purpose of writing this thesis is to understand the application procedures and responsibilities of guardians in processing permits to sell assets of minors in the District Court. This research uses a normative juridical approach, namely, it is carried out by examining theoretical concepts and statutory regulations related to this writing. The data source for this research is a secondary data source, namely data obtained through literature study. The method used in data analysis is a qualitative method, namely interpreted logically and systematically and then conclusions are drawn. The results of this research show that the application submission process consists of: first, the administrative stage, namely: the applicant brings the application letter, submits the case files to the first desk to register the application, pays the down payment, the First Desk Officer submits the SKUM and a copy of the application. Second, the trial stage, namely: The Panel of Judges reads the petition along with the evidence and grants the petitioner's petition. The guardian's responsibility is to make a list of the child's assets under his or her control and record all changes in assets used for the child's benefit until the end of the guardianship period.

Immunotherapy of malignant gliomas: a modern view on the problem

Malignant gliomas are one of the most common brain tumors in adults arising from glial cells with an extremely poor prognosis. Generally, therapy of malignant gliomas consists of radical surgical removal followed by radio- and/or chemotherapy. However, prognosis of the disease remains unfavorable.The review presents main clinical, morphological and molecular characteristics of gliomas, their prognostic significance and role in the choice of targeted therapy based on using tyrosine kinase inhibitors and/or monoclonal antibodies. The current aspects of immunotherapy of gliomas (i.e., activation of immune cells, or blockage of immunosuppressive signaling) are discussed in detail. One of the well-known approaches of cancer immunotherapy is based on immune checkpoint inhibitors. These drugs might be effective in treatment of malignant gliomas overexpressing the molecules that suppress immune cells functions. Another promising approach of gliomas immunotherapy is based on genetically modified CAR-T cells (CAR – chimeric antigen receptor) which might identify and eliminate cancer cells. Cytokine therapy is also perspective treatment approach, as well as gene therapy which is associated with editing viral genes for production of oncolytic viruses used as anticancer vaccines. Vaccines are being developed to generate the specific antibodies recognized cancer cells and thereby stimulate the immune system to identify and destroy tumor cells.Despite the promising potential of various gliomas immunotherapy methods, most of them are at different stages of preclinical and clinical trials. Some of them demonstrate promising results and good perspective for the further use to treat glioma patients.

Prospects of Inhalable Formulations of Conventionally Administered Repurposed Drugs for Adjunctive Treatment of Drug-Resistant Tuberculosis: Supporting Evidence from Clinical Trials and Cohort Studies.

Background: Drug resistant tuberculosis is a major public health concern, since the causative agent Mycobacterium tuberculosis is resistant to the most effective drugs against tuberculosis treatment ie., rifampicin and isoniazid. Globally, it accounts 4.6 percent of the patients with tuberculosis, but in some low socioeconomic areas this proportion exceeds to 25 percent. The treatment of drug resistant tuberculosis is prolonged (9-12 months) and often have less favorable outcome with novel as well as recently repurposed drugs administered by conventional routes. Materials and Methods: Clinically, these repurposed drugs have shown several major concerns including low penetration of the drugs to the pulmonary region, emergence of resistant forms, first pass effects, drug-drug interactions, food effects, and serious side effects upon administration by conventional route of administration. Although, several antimicrobial agents have been either approved or are under investigation at different stages of clinical trials and in pre-clinical studies via inhalation route for the treatment of respiratory infections, inhalable formulation for the treatment of drug resistant tuberculosis is most untouched aspect of drug delivery to validate clinically. Only a single dry powder inhalation formulation of capreomycin is able to reach the milestone, ie., phase I for the treatment of drug resistant tuberculosis. Results: Administering inhalable formulations of repurposed drugs as adjuvant in the treatment of drug resistant tuberculosis could mitigate several concerns by targeting drugs directly in the vicinity of bacilli. Conclusion: This review focuses on the limitations and major concerns observed during clinical trials of repurposed drugs (host directed or bactericidal drugs) administered conventionally for the treatment of drug resistant tuberculosis. The outcomes and the concerns of these clinical trials rationalized the need of repurposing formulation which could be administered by inhalation route as adjunctive treatment of drug resistant tuberculosis. [Figure: see text].

PENERAPAN SANKSI PIDANA TERHADAP ANAK PENYALAHGUNAAN SENJATA TAJAM STUDI DI KEPOLISIAN RESORD DOMPU

Crime is a social phenomenon that is always inherent in every human life so that every development of the times will have an influence on social change in society. One of the crime phenomena that occurs due to social change is the misuse of sharp weapons by children in Dompu Regency in the jurisdiction of the Dompu Resort Police. The purpose of this study is to determine the application of sanctions against children who misuse sharp weapons in the Dompu Police Department. The research method used is a type of empirical research that examines the facts that occur in the field with a statute approach and case approach. The results showed that the application of criminal sanctions against children who misuse sharp weapons in the Dompu Resort Police was resolved by diversion through restorative justice with the result that the child was returned to the parents to be given guidance and supervision by the parents so as not to repeat their actions. In addition to diversion, children who misuse sharp weapons that are declared P21 (complete file) are forwarded to the Public Prosecutor for further processing, namely the trial stage. The Dompu Police Department, especially the Women and Children Protection Unit, has carried out its duties properly

Efficient Positioning of QTL and Secondary Limit Thresholds in a Clinical Trial Risk-Based Monitoring.

In the high-stakes world of clinical trials, where a company's multimillion-dollar drug development investment is at risk, the increasing complexity of these trials only compounds the challenges. Therefore, the development of a robust risk mitigation strategy, as a crucial component of comprehensive risk planning, is not just important but essential for effective drug development, particularly in the RBQM (Risk-Based Quality Management) ecosystem and its component-RBM (Risk-Based Monitoring). This emphasis on the urgency and significance of risk mitigation strategy can help the audience understand the gravity of the topic. The paper introduces a novel modeling framework for deriving an efficient risk mitigation strategy at the planning stage of a clinical trial and establishing operational rules (thresholds) under the assumption that contingency resources are limited. The problem is solved in two steps: (1) Deriving a contingency budget and its efficient allocation across risks to be mitigated and (2) Deriving operational rules to be aligned with risk assessment and contingency resources. This approach is based on combining optimization and simulation models. The optimization model aims to derive an efficient contingency budget and allocate limited mitigation resources across mitigated risks. The simulation model aims to efficiently position each risk's QTL/KRI (Quality Tolerance Limits/Key Risk Indicators at a clinical trial level) and Secondary Limit thresholds. A case study illustrates the proposed technique's practical application and effectiveness. This example demonstrates the framework's potential and instills confidence in its successful implementation, reassuring the audience of its practicality and usefulness. The paper is structured as follows. (1) Introduction; (2) Methodology; (3) Models-Risk Optimizer and Risk Simulator; (4) Case study; (5) Discussion and (6) Conclusion.

In Vivo Cardiovascular Molecular Imaging: Contributions to Precision Medicine and Drug Development.

Conventional forms of noninvasive cardiovascular imaging that evaluate morphology, function, flow, and metabolism play a vital role in individual treatment decisions, often based on guidelines. Innovations in molecular imaging have enhanced our ability to spatially quantify the expression of a wider array of disease-related proteins, genes, or cell types, or the activity of specific pathogenic pathways. These techniques, which usually rely on design of targeted imaging probes, have already been used extensively in cancer medicine and have now become part of cardiovascular care in conditions such as amyloidosis and sarcoidosis. The recognition that common cardiovascular conditions are caused by a substantial diversity of pathobiologic pathways and the diversity of therapies available for use have rekindled interest in expanding the role of molecular imaging of tissue phenotype to improve precision in diagnosis and therapeutic decision-making. The intent of this article is to raise awareness and understanding of approaches to molecular or cellular imaging of phenotype with targeted probes, and their potential to promote the principles of precision medicine. Also addressed are the diverse roles of molecular imaging to improve precision and efficiency of new drug development at the stages of candidate identification, preclinical testing, and clinical trials.

Patient Perceptions of Emerging Gene Therapies for Arrhythmogenic Right Ventricular Cardiomyopathy.

No disease-specific therapy currently exists for arrhythmogenic right ventricular cardiomyopathy (ARVC), a progressive cardiogenetic condition conferring elevated risk for ventricular arrhythmias, heart failure, and sudden cardiac death. Emerging gene therapies have the potential to fill this gap. However, little is known about how adults with ARVC, or any other inherited cardiomyopathy or arrhythmia syndrome, appraise the risks and benefits of gene therapy research and which considerations may influence their decisions about clinical trial participation. Twenty adults with clinically diagnosed and gene-positive ARVC participated in semistructured interviews that explored perceptions of gene therapy and hypothetical decision-making for gene therapy clinical trial participation. Interview transcripts were qualitatively coded and analyzed. Participants expressed enthusiasm for gene therapy with varied levels of personal interest in trial participation. Although clinical severity appeared to be associated with an elevated interest in early trial participation, participants anticipated weighing both personal and trial-specific factors including life stage, trial stage, risks, benefits, participation burden, study leadership, and anticipated cost of future gene therapy. Adaptation to living with ARVC and involvement in the ARVC patient community were also relevant to decision-making about trial participation. Potential ethical concerns included unquestioning trust in clinical teams collaborating on industry-led trials and vulnerability of those recently diagnosed or with high perceived severity of ARVC symptoms. Several characteristics of the individual and trial warrant consideration during the informed consent process. Insights from this study may affect trial planning and communication with participants who have inherited cardiac conditions.

The many faces of DGAT1.

Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) is a multifaced enzyme with a wide spectrum of substrates, from lipids through waxes to retinoids, which makes it an interesting therapeutic target. DGAT1 inhibitors are currently at various stages of preclinical and clinical trials, mostly related to metabolic diseases. Interestingly, in recent years, a growing amount of research has shown the influence of DGAT1 on immune cell metabolism and functions, highlighting its important role during infections and tumorigenesis. In this review, we aim to elucidate the potential immunomodulatory effect of DGAT1 in physiological and pathological conditions.

RNA-based Therapeutics: Past, Present and Future Prospects, Challenges in Cancer Treatment.

It is becoming more and harder in today's climate to disregard the impact of cancer on social health. Even though a significant amount of money is spent annually on cancer research, it still ranks as the second leading cause of death worldwide. Additionally, only about half of the patients suffering from complex forms of cancer survive a year after receiving traditional cancer therapies. A method for silencing genes is called RNA interference (RNAi). Such a method is very effective in focusing on genes linked to cancer. Most gene products implicated in cancer have recently been used as RNA interference (RNAi) therapeutic targets. According to the findings from this research, RNAi application is necessary for today's cancer treatment to target functioning carcinogenic molecules and tumor resistance to chemotherapy and radiation. Proapoptotic and antiproliferative activity has been reported from previous research studies on cell culture systems, animal models, and clinical trials through the knockdown of gene products from RNAi technology. Numerous novel RNAi-based medications are now in the clinical trial stages thanks to the discovery of the RNAi mechanism and advancements in the area. In the future, genomic-based personalized medicines can be developed through this RNAi therapy. Hopefully, cancer sufferers will find this sort of therapy to be one of the most effective ones. Various kinds of RNA-based treatments, such as aptamers, small interfering RNAs, microRNAs, antisense oligonucleotides, and messenger RNA, are covered in broad terms in this study. We also present an overview of the RNA-based therapies that have received regulatory approval in the past or are now undergoing clinical studies.

Development of Project Based Learning Media Using Google Sites on Alternative Energy Topics

<p>Learning is carried out to arrange and organize the environment around students to foster their learning process. The student's learning process is carried out through inquiry, responding to questions regarding a problem or a complex challenge. This learning process can be conducted by applying the project-based learning model. The project-based learning model can be applied in the field of information and communication technology in line with the 21<sup>st</sup> century, such as using Google Sites. Therefore, this research aims to describe the specifications of Google Sites as a learning media using the project-based learning model on alternative energy topics and describe the assessment results from experts, educational practitioners, and learners regarding Google Sites as a learning media using the project-based learning model on alternative energy materials. This development research employs the 4D model by Thiagarajan, which consists of the following stages: define, design, develop, and disseminate. The learning media obtained validation from two experts and assessment from educational practitioners regarding content, media, and language aspects. The development trial of this media was conducted with phase E students. Data collection techniques included interviews and questionnaires, with data analysis performed qualitatively and quantitatively. The learning media comprises a primary topic, alternative energy, organized based on project-based learning syntax. It consists of three menus: the welcome menu, the main page, and the author's identity. Validation by experts and assessment by educational practitioners indicate that the learning media meets excellent content, media, and language criteria. The development trial results show that the learning media meets excellent criteria at each trial stage.</p>

Evaluating multiplicity reporting in analgesic clinical trials: An analytical review.

Analgesia trials often demands multiple comparisons to assess various treatment arms, outcomes, or repeated assessments. These multiple comparisons risk inflating the false positive rate. Multiplicity correction in recent analgesic randomized controlled trials (RCTs) remains unclear despite statistical method advancements and regulatory guidelines. Our study aimed to identify reporting inadequacies in multiple analysis adjustments and explanations to understand these deficiencies. This review analysed RCTs from the European Journal of Pain, the Journal of Pain, and PAIN, published between January 2018 and December 2022. We included randomized, double-blind trials focusing on pain outcomes. Data extraction, managed by three researchers using predefined criteria, included trial characteristics, multiplicity presence, and correction methods. Descriptive statistical analyses included Fisher's exact, and Holm method for multiple comparisons. Out of 112 articles, 48 pre-specified a primary analysis plan. Multiple analyses were observed in 65 articles, with 60% adjusting for all comparisons, primarily using the Bonferroni method. Compared with previous studies, no significant changes in multiplicity correction practices were noted when stratified by trial type, size, and sponsor. The study reveals a persistent reliance on multiple comparisons in analgesic clinical trials without a corresponding increase in multiplicity corrections emphasizing a need for enhanced reporting and implementation of statistical adjustments. We acknowledge limitations in categorizing studies, the use of a surrogate for the trial stage, and sourcing data from journal webpages rather than a database. This study flags inadequate reporting on multiplicity correction in analgesic trials, stressing the risk of false positives and the urgent need for enhanced reporting to boost reproducibility.