Research Clinical Experience Research Articles

A framework for N-of-1 trials of individualized gene-targeted therapies for genetic diseases.

Individualized genetic therapies-medicines that precisely target a genetic variant that may only be found in a small number of individuals, as few as only one-offer promise for addressing unmet needs in genetic disease, but present unique challenges for trial design. By nature these new individualized medicines require testing in individualized N-of-1 trials. Here, we provide a framework for maintaining scientific rigor in N-of-1 trials. Building upon best practices from traditional clinical trial design, recent guidance from the United States Food and Drug Administration, and our own clinical research experience, we suggest key considerations including comprehensive baseline natural history, selection of appropriate clinical outcome assessments (COAs) individualized to the patient genotype-phenotype for safety and efficacy assessment over time, and specific statistical considerations. Standardization of N-of-1 trial designs in this fashion will maximize efficient learning from this next generation of targeted individualized therapeutics.

Cross-sectional exploratory survey among health researchers in Europe on the awareness of and barriers affecting the use of an evidence-based research approach

ObjectivesThis exploratory study was conducted to find out how well the concept of evidence-based research (EBR) is known among European health researchers with substantial clinical research experience, and which barriers...

PCR47 Characterization of Variability in Response Set Composition Across Pros: Insights for Reducing Complexity and Improving the Patient Experience of Clinical Research

PCR47 Characterization of Variability in Response Set Composition Across Pros: Insights for Reducing Complexity and Improving the Patient Experience of Clinical Research

Piloting electronic informed consenting in a pneumococcal human infection study in Blantyre, Malawi

Background Electronic consent can potentially improve accuracy, workflow, and overall patient experience in clinical research but has not been used in Malawi, owing to uncertainty about data security and technical support. Objectives We explored the feasibility of using electronic consent (e-consent) in an ongoing human infection study in Blantyre Malawi. We dual-consented participants by both electronic and paper methods to assess the feasibility of electronic consent, and then compared benefits and challenges of the two methods. Methods The approved paper consent forms were digitized using Open Data Kit (ODK). Following participant information giving by the research staff, healthy literate adult participants with no audio-visual impairments completed a self-administered e-consent and provided an electronic signature. Signed e-consent forms were uploaded to a secure study server. While the participants were in clinic, the signed electronic consent form was printed as a copy for the participant. The feasibility, advantages and disadvantages including data safety consideration for e-consenting were evaluated by exploring issues surrounding use of e-consenting versus paper-based consenting. Consent forms were analysed by research staff for errors such as overwriting and legibility. Results We piloted 109 participants to e-consenting. It was found to be user friendly, had 0% (n 0/109) errors compared to 43.1% (n 47/109) in paper based methods along with enhanced data safety. The challenges included difficult digitization of ethics stamped documents, volunteer unfamiliarity with tablet user interface and its requirement for a working internet and printer. Conclusion E-consenting was feasible but required additional resource investment. Benefits included error minimization and data security.

Data on Ocrelizumab Treatment Collected by MS Patients in Germany Using Brisa App.

With a rising number of multiple sclerosis (MS) cases and increasing pressure on health systems, digital companion apps like Brisa, designed specifically for people with MS, can play an important role in the patient journey. These apps enable the collection of real-time longitudinal data that are critical to our understanding of the pathophysiology and progression of MS. This retrospective, descriptive analysis consists of data from Brisa users who registered between 6 August 2021 and 8 September 2022. Of the unique users, 37.7% (n = 1593) fulfilled the inclusion criteria including information about medication and demographics and tracked one or more symptoms and/or patient-reported outcomes. Users were classified as moderate-efficacy treatment users, high-efficacy treatment users and ocrelizumab users, and the reporting frequency and scores of symptoms and patient-reported outcomes were analyzed. The largest cohort of Brisa users (405) reported treatment with ocrelizumab and were mostly diagnosed 2-5 years before the survey. The most reported MS symptoms were similar between OUs (ocrelizumab users), HETUs (high-efficacy treatment users) and METUs (moderate-efficacy treatment users). OUs on average reported symptoms and answered questionnaires more frequently. Baseline scores between HETUs and OUs were similar, whereas baseline scores of METUs were slightly lower in comparison. In a further analysis of OUs, disability scores increased with age; users aged 26-45 years had higher pain scores than 18-25-year-olds. No significant differences were found in quality of life, bowel control and vision between age groups. These findings show that the characteristics of the Brisa cohort are similar to the results of other studies and registries and can provide a representative overview of everyday disease management. Thereby, these results can bridge the gap between clinical research and real patient experience, but they also raise new questions, such as how often the hard-and-early therapy approach is already used and whether baseline characteristics and reasons for choosing a particular treatment contribute to the different outcomes over time. Answering these questions requires further research and analysis.

ICU Care Team's Perception of Clinical Research in the ICU: A Cross-Sectional Study.

Adequate recruitment is essential for successful clinical research. ICU nurses play a crucial role in identifying eligible patients, introducing research teams, facilitating informed consent, and caring for enrolled patients. However, a larger group of multidisciplinary healthcare professionals (the ICU care team) is equally important in promoting clinical research participation.To describe the ICU care team's experiences in ongoing clinical research, identifying perceived barriers and enablers to their participation, and apply a behavior framework to enhance research engagement. Cross-sectional survey study. Four adult ICUs and one PICU between June 2021 and March 2023. We recruited nurses, physicians, nurse practitioners, allied health professionals, and unit clerks. We developed and validated a cross-sectional survey based on the Capability, Opportunity, Motivation, Behavior model. This survey included: 1) demographic questions (n = 7); 2) research experience questions (n = 6), 3) capability questions (n = 8); 4) opportunity questions (n = 11); 5) and motivation questions (n = 13).A total of 172 ICU care team members completed the survey. Results showed differences in capabilities, opportunities, and motivations among ICU care team members. For example, fellow/attending physicians and nurse practitioners reported higher confidence in discussing research with patients/families, while registered nurses and allied health professionals expressed less confidence. ICU care team members face multiple barriers that impact their involvement with the conduct of ICU research. To effectively engage healthcare professionals in this process, it is essential to address their capabilities (research knowledge and skills to communicate research with patients/families), create opportunities (collaboration/communication with research team, discuss research during multidisciplinary rounds), and motivate them (recognize their help and share the results of the research being conducted at their site) to improve ICU care team engagement in the conduct of ICU research.

120 Impact of Undergraduate Clinical Research Experience: Highlighting the UCLA Clinical and Translational Science Institute Research Associates Program (CTSI-RAP)

OBJECTIVES/GOALS: CTSI-RAP is a professional development program that provides undergraduate students with clinical research exposure and training. Students support UCLA research faculty by assisting with all aspects of the research process, including recruiting participants, data management, and presentations. METHODS/STUDY POPULATION: CTSI-RAP onboards a 15-20 volunteer student cohort annually in a competitive application and interview process with less than a 10% acceptance rate. Since the inaugural cohort in 2013, over 160 students have participated. The program engages hundreds of students each year through the recruitment process, campus clinical research events, and student-led conference opportunities. Evaluation surveys developed through REDCap in 2022 sought to assess the program’s impact on undergraduate experiences, professional development, and post-graduate careers. Surveys distributed to investigators and their study teams evaluated the student’s clinical research knowledge and engaged student involvement. RESULTS/ANTICIPATED RESULTS: Based on evaluation surveys, the CTSI-RAP program received excellent reviews from both students and their assigned study teams. 100% of students and faculty would recommend the program to a friend or colleague. 30% of students present or publish annually, indicating a wealth of meaningful contributions made by students. 90% of students go on to attend medical school, health-related graduate school, or other health-related employment. Several students continue working in clinical research through gap-year employment. As demonstrated by the high caliber of student and faculty experiences, CTSI-RAP has created an esteemed and valued symbiotic infrastructure to support clinical research endeavors at UCLA. DISCUSSION/SIGNIFICANCE: Through clinical research career exploration and professional skill-building in undergraduate careers, the CTSI-RAP program produces highly-trained future leaders in the field and benefits the capacity of UCLA research. CTSI-RAP provides a model for similar programs to be funded and implemented in other institutions.

Abstract 999: Clinical trial matchmaking: Connecting sites to sponsors

Abstract Background: Oncology programs may encounter many challenges engaging in clinical trials. The Association of Community Cancer Center’s (ACCC) Community Oncology Research Institute (ACORI) conducted a survey to gather insights on barriers to clinical trial provision and implementation, patient recruitment, and identifying resources to support cancer programs. Methods: A survey of 29 questions was administered via Qualtrics. The survey focused on research-naïve sites (i.e., sites with little to no clinical research experience). Survey recipients were identified from ACCC’s membership database, and the survey was open from May 5 to October 10, 2023. One survey response was captured per program. Results: Of the 350 respondents, most were physicians, investigators, or oncology fellows (20%), directors/administrators (16%), patient navigators (12%), and APPs (12%). Responding programs were categorized as a comprehensive community cancer program (28%), community practice (26%), or academic medical center (21%). Eighty percent of respondents indicated their program currently conducts clinical research. The most common challenges included: patient recruitment (40%), limited staffing (36%), limited clinician time (32%), and lack of training in research administration and conduct (25%). The top 3 resources desired were communication about clinical research opportunities (65%), connections to clinical trial sponsors (49%), and clinical research coordinator training (41%). Conclusions: Survey results showed a clear need for improved communication regarding clinical research opportunities, connections to clinical trial sponsors, and education around clinical trial implementation. Data from this survey will be used to match sites with trial sponsors, especially sites that serve patients with cancer from under resourced geographic, socioeconomic, racial, and ethnic groups. Future efforts will seek to engage clinical trial sponsors in improving trial engagement and feasibility, workforce support, training, and clinical mentorship. Citation Format: Lyndsey Griffin, Latha Shivakumar, Leigh Boehmer, Savannah Dodson, Elana Plotkin, Sumanta Pal, Al B. Benson. Clinical trial matchmaking: Connecting sites to sponsors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 999.

Automated Calculator for the Pediatric Sequential Organ Failure Assessment Score: Development and External Validation in a Single-Center 7-Year Cohort, 2015-2021.

The pediatric Sequential Organ Failure Assessment (pSOFA) score summarizes severity of organ dysfunction and can be used to predict in-hospital mortality. Manual calculation of the pSOFA score is time-consuming and prone to human error. An automated method that is open-source, flexible, and scalable for calculating the pSOFA score directly from electronic health record data is desirable. Single-center, retrospective cohort study. Quaternary 40-bed PICU. All patients admitted to the PICU between 2015 and 2021 with ICU stay of at least 24 hours. None. We used 77 records to evaluate the automated score. The automated algorithm had an overall accuracy of 97%. The algorithm calculated the respiratory component of two cases incorrectly. An expert human annotator had an initial accuracy of 75% at the patient level and 95% at the component level. An untrained human annotator with general clinical research experience had an overall accuracy of 16% and component-wise accuracy of 67%. Weighted kappa for agreement between the automated method and the expert annotator's initial score was 0.92 (95% CI, 0.88-0.95), and between the untrained human annotator and the automated score was 0.50 (95% CI, 0.36-0.61). Data from 9146 patients (in-hospital mortality 3.6%) were included to validate externally the discriminability of the automated pSOFA score. The admission-day pSOFA score had an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.77-0.82). The developed automated algorithm calculates pSOFA score with high accuracy and is more accurate than a trained expert rater and nontrained data abstracter. pSOFA's performance for predicting in-hospital mortality was lower in our cohort than it was for the originally derived score.

A global pilot comparative, cross-sectional study of clinical research nurses/research midwives: Definition, knowledge base, and communication skills related to the conduct of decentralized clinical trials.

A gap in the literature exists pertaining to a global research nurse/research midwife resources and communication skill set necessary to engage with participants of diverse populations and geographic regions in the community or home-based conduct of decentralized clinical trials. An embedded mixed methods study was conducted to examine research nurse/research midwife knowledge base, experiences, and communication skill sets pertaining to decentralized trials across global regions engaged in remote research: the USA, Republic of Ireland, United Kingdom, and Australia. An online survey was deployed across international research nurse/research midwife stakeholder groups, collecting demographics, decentralized trial experience, barriers and facilitators to optimal trial conduct, and the self-perceived communication competence (SPCC) and interpersonal communication competence (IPCC) instruments. 86 research nurses and research midwives completed the survey across all countries: The SPCC and IPCC results indicated increased clinical research experience significantly correlated with increased SPCC score (p < 0.05). Qualitative content analysis revealed five themes: (1) Implications for Role, (2) Safety and Wellbeing, (3) Training and Education, (4) Implications for Participants, and (5) Barriers and Facilitators. Common trends and observations across the global sample can inform decentralized trial resource allocation and policy pertaining to the research nurse/research midwife workforce. This study demonstrates shared cultural norms of research nursing and midwifery across varied regional clinical trial ecosystems.

Pragmatic design and inclusion of patient-partner representatives improves participant experience in clinical research.

Patient engagement in the design and implementation of clinical trials is necessary to ensure that the research is relevant and responsive to patients. The PREP-IT trials, which include 2 pragmatic trials that evaluate different surgical preparation solutions in orthopaedic trauma patients, followed the patient-centered outcomes research (PCOR) methodology throughout the design, implementation, and conduct. We conducted a substudy within the PREP-IT trials to explore participants' experiences with trial participation. At the final follow-up visit (12 months after their fracture), patients participating in the PREP-IT trials were invited to participate in the substudy. After providing informed consent, participants completed a questionnaire that asked about their experience and satisfaction with participating in the PREP-IT trials. Descriptive statistics are used to report the findings. Four hundred two participants participated in the substudy. Most participants (394 [98%]) reported a positive experience, and 376 (94%) participants felt their contributions were appreciated. The primary reasons for participation were helping future patients with fracture (279 [69%]) and to contribute to science (223 [56%]). Two hundred seventeen (46%) participants indicated that their decision to participate was influenced by the minimal time commitment. Most participants reported a positive experience with participating in the PREP-IT trials. Altruism was the largest motivator for participating in this research. Approximately half of the participants indicated that the pragmatic, low-participant burden design of the trial influenced their decision to participate. Meaningful patient engagement, a pragmatic, and low-burden protocol led to high levels of participant satisfaction.

New technology and research progress in neurosurgery diagnosis and treatment

Neurosurgery is a vital branch of medicine that deals with the surgical management of brain disorders. The increasing demand for clinical solutions drives technological innovation, and the rapid progress in science and technology enables new discoveries, knowledge, techniques, and instruments in neurosurgery, expanding the scope and accuracy of diagnosis and treatment, and enhancing therapeutic outcomes. The author team combines domestic and international literature and previous clinical and scientific research experience, focusing on practical clinical problems in several subspecialties, including neuroimaging, neuronavigation and surgical robot assistance, central nervous system tumors, surgical treatment of cerebrovascular disease, functional neurosurgery, neuroinjury and neural repair, and digital neurosurgery. The paper summarizes in detail the research hotspots and puts forward the research direction prospects, including the innovative application of imaging technology, the development of fine surgery, the innovation of neuro-oncology diagnosis and treatment, the surgical standardization of cerebrovascular disease, the progress of neuromodulation, the individualized neurological alternative treatment and the digitalization of multi-dimensional information in neurosurgery.

The evidence-based practice teaching competence of clinical preceptors at different stages of innovation-decision process: A cross-sectional survey in traditional Chinese medicine hospitals

BackgroundTraditional Chinese Medicine Nursing Clinical Preceptors (TCMN-CPs) are crucial to cultivate undergraduates' evidence-based practice (EBP) competence during clinical practicum in traditional Chinese Medicine (TCM) hospitals. However, the TCMN-CPs' EBP teaching competence is unclear. Underpinned by Rogers' innovation-decision process, our study aimed to investigate TCMN-CPs' EBP teaching competence and the related characteristic factors at five stages of knowledge, persuasion, decision, implementation and confirmation. MethodsAn online survey was conducted by using a modified evidence-based practice teaching competence questionnaire (EBPT-COQ) encompassing attitude, knowledge/skill and practice of EBP teaching in four TCM teaching hospitals in Beijing, China. ResultsA total of 654 TCMN-CPs were included, with a response rate of 91.47 %. Most TCMN-CPs were in knowledge stage (339, 51.83 %), followed by the persuasion stage (166, 25.38 %), decision stage (123, 18.81 %), implementation stage (23, 3.52 %) and confirmation stage (3, 0.46 %). The total and dimension scores of EBPT-COQ increased as the diffusion stage developing, the confirmation stage was the highest (5.48 ± 0.80). Twenty-three items' mean scores were higher than 4 points (95.83 %), except for “Research skills” (3.58 ± 1.38). The related characteristic factors were 1) age (Z = -4.177), working experience (H = 11.087), clinical teaching experience (H = 12.602), management position (Z = 2.565), research experience (Z = -2.867) and EBP training (Z = 3.146) at Knowledge stage; 2) research experience (ZPersuasion = −2.617; ZDecision = −3.510), EBP training (ZPersuasion = 2.528; ZDecision = 3.433) at Persuasion and Decision stage (all P<0.05). And the first three stages TCMN-CPs' EBPT-COQ scores were positively correlated with TCMN-CPs' attitude toward clinical teaching (r = 0.244–0.331, P<0.001). ConclusionsMost of the TCMN-CPs' EBP teaching status are in the first three diffusion stages. Though their attitude, knowledge/skills and practice to EBP teaching competence have gradually improved with the deepening of the diffusion stage, much efforts should be made to keep progressing. TCMN-CPs' qualifications of EBP teaching could include rich clinical work and teaching experience, enjoying teaching. Nursing managers, with higher EBP teaching competence, might play a crucial role in promoting the diffusion of EBP teaching. All TCMN-CPs showed an inadequacy of research skills of EBP teaching. Therefore, it is warranted to explore the minimum research skill requirements for EBP teaching and to establish academic-practice partnerships.

The carbon footprint of clinical trials: a global survey on the status quo and current regulatory guidance

IntroductionAll economic sectors including the service sector, along with healthcare, education and research, need to reduce their greenhouse gas emissions to limit global temperature increases. In this study, we aim...

Cryobiology and Cryomedicine Techniques’ Boosting in Wartime

The review surveys the published data on a strong negative impact of psycho-emotional stress, which accompanies both the military servicemen and civilians of any state in martial law period. Such a load can lead to severe disorders of the systems that ensure the human body homeostatic stability, in particular to post-traumatic stress disorder. In this case human body is subjected to a state accompanied by the development of severe oncology and autoimmune diseases, as well as dysfunction of the male reproductive system. The study offers modern approaches to the treatment of the listed pathologies, most of which are based on the international experience of clinical and experimental research as well as achievements of national academic science. Special attention is paid to the development of cryobiological and cryomedical cell-tissue techniques, the use of those can be promising in the strengthening of both mental and physical health of civilian population during the wartime.

Methotrexate for inflammatory skin disease in pediatric patients: Consensus treatment guidelines.

Methotrexate (MTX) is a readily accessible drug, first used in 1948 and employed for a wide variety of indications since then. However, despite widespread off-label use, FDA labeling does not include approved indications for the use of MTX for many inflammatory skin diseases in pediatric patients, including morphea, psoriasis, atopic dermatitis, and alopecia areata, among others. Without published treatment guidelines, some clinicians may be hesitant to use MTX off-label, or uncomfortable prescribing MTX in this population. To address this unmet need, an expert consensus committee was convened to develop evidence- and consensus-based guidelines for use of MTX to treat pediatric inflammatory skin disease. Clinicians with experience and expertise in clinical research, drug development, and treating inflammatory skin disease in pediatric patients with MTX were recruited. Five committees were created based on major topic areas: (1) indications and contraindications, (2) dosing, (3) interactions with immunizations and medications, (4) adverse effects (potential for and management of), and (5) monitoring needs. Pertinent questions were generated and addressed by the relevant committee. The entire group participated in a modified Delphi process to establish agreement on recommendations for each question. The committee developed 46 evidence- and consensus-based recommendations, each with >70% agreement among members, across all five topics. These are presented in tables and text, along with a discussion of supporting literature, and level of evidence. These evidence- and consensus-based recommendations will support safe and effective use of MTX for the underserved population of pediatric patients who may benefit from this valuable, time-honored medication.

Road resilience: adaptive education for emerging challenges

The reality of paramedicine can cause students emotional distress, especially if this tests their values or beliefs. Therefore, educating students to be resilient and prepared for unpredictable, distressing events should be considered. The need to increase professional longevity in paramedicine has shifted employers' focus from road readiness to road resilience, which presents a complex challenge for educators. This article is the first of a series to discuss the use of supporting sciences to build road resilience in undergraduate paramedicine programmes. A review of the literature on paramedic education demonstrates there is new knowledge, based on experience in clinical practice and research, that paramedic educators can draw on to develop their discipline. Paramedics with postgraduate qualifications can shape the future of their professional discipline when their research produces a new discourse that informs a curriculum which can meet contemporary challenges. Discussion of a fictional case study illustrates how an emotional crisis could provide a platform for reflective learning and make a student more effective as a paramedic, and the educational environment needed to facilitate this.

P086 The French clinical research network in cystic fibrosis more than 10 years of positive experience in clinical research for patients

P086 The French clinical research network in cystic fibrosis more than 10 years of positive experience in clinical research for patients

Cultural Change, Community, and Belonging: Supporting the Next Generation of Surgeons From Groups Historically Excluded From Medicine.

Cultural Change, Community, and Belonging: Supporting the Next Generation of Surgeons From Groups Historically Excluded From Medicine.

The Influence of Anti-LGBTQIA+ Legislation on Graduate Medical Education

The Influence of Anti-LGBTQIA+ Legislation on Graduate Medical Education