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BACKGROUND: Clinical trials are categorized as industry sponsored trials (ISTs) or investigator-initiated trials (IITs) based on the source of funding and sponsor of the trial. ISTs are usually run by pharmaceutical companies, and are primarily aimed at developing new drugs that ultimately gain regulatory approval. IITs are developed by academic investigators or cooperative groups, often sparked by a clinical need. Both are vital in advancing the field of oncology. To date, little has been published about current trends in ISTs or IITs in genitourinary (GU) oncology. The aim of this study was to assess growth trends of GU oncology ISTs and IITs in 4 countries with similar healthcare infrastructures. METHODS: We searched ClinicalTrials.gov for bladder, kidney, and prostate cancer trials conducted in the United States (US), Canada, France, and United Kingdom (UK) from January 2007 to December 2021. Trials were determined to be ISTs or IITs based on their funding source and sponsor. Trials were characterized based on type, purpose, phase, participants, masking, assignment, and allocation. RESULTS: Overall, 5,834 GU trials were identified, with a balanced distribution of ISTs (n = 3064, n = 52.5%) and IITs (n = 2770, 47.4%). By country, the US conducted the most GU trials (n = 3814) followed by Canada (n = 709), France (n = 677), and the UK (n = 634). Most ISTs were phase 3 trials with over 500 participants while most IITs were open-label phase 2 studies with only 20-49 participants. From 2017 onwards, there was a shift towards more ISTs, most noticeably in Canada and the UK. The COVID-19 pandemic did not have a major impact on the growth of ISTs and IITs. CONCLUSION: The gap between ISTs and IITs continues to widen, likely driven by resource and funding challenges faced by investigators. Barriers to completing IITs need to be better understood to promote IIT development and maintain their academically driven intentions.

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INTRODUCTION: Addressing the public health problem of physical inactivity, this study evaluates "SNapp", a just-in-time adaptive app intervention to promote walking through dynamically tailored coaching content. It assesses SNapp's impact on daily steps and how users' perceptions regarding ease of use and usefulness moderated its effectiveness. STUDY DESIGN: SNapp was evaluated in an RCT from February 2021 to May 2022. Analyses were conducted in November 2022. SETTING/PARTICIPANTS: 176 adults (76% female, mean age of 56 years) were randomized to a control group receiving a step counter app (n = 89) or an intervention group receiving the app plus coaching content (n = 87). INTERVENTION: SNapp's coaching content encompasses individually tailored feedback on step counts and advice to engage in more walking, taking preferences regarding behavior change techniques into account. Additionally, SNapp provides contextualized content calling attention to suitable walking locations in the user's environment. MAIN OUTCOME MEASURES: The primary outcome was daily step count as recorded by the step counter app. User perceptions regarding ease of use and usefulness were assessed via survey at 3-month follow-up. RESULTS: Mixed models indicated that the intervention did not significantly impact step counts on average over time (B = -202.30, 95% CI = -889.7, 485.1), with the coefficient indicating that the intervention group walked fewer steps per day on average, though this difference was not statistically significant. Perceived ease of use did not moderate the intervention effect (B group x perceived ease of use = 38.60, 90% CI = -276.5, 353.7). Perceived usefulness significantly moderated the intervention effect (B group x perceived usefulness = 344.38, 90% CI = 40.4, 648.3). CONCLUSIONS: SNapp increased steps only in users who deemed the app useful, underscoring the importance of user perceptions in app-based interventions. TRIAL REGISTRATION: This trial was preregistered in the Dutch Trial Register (NL7064).

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BACKGROUND AND OBJECTIVES: Although the goal of translational research is to bring biomedical knowledge from the laboratory to clinical trial and therapeutic products for improving health, this goal has not been well achieved as often as desired because of many barriers documented in different countries. Therefore, the aim of this study was to investigate the challenges and opportunities of translating animal research into human trials in Ethiopia. METHODS: A descriptive qualitative study, using in-depth interviews, was conducted in which preclinical and clinical trial researchers who have been involved in animal research or clinical trials as principal investigator were involved. Data were analyzed using inductive thematic process. RESULTS: Six themes were emerged for challenges: lack of financial and human capacity, inadequate infrastructure, operational obstacles and poor research governance, lack of collaboration, lack of reproducibility of results and prolonged ethical and regulatory approval processes. Furthermore, three themes were synthesized for opportunities: growing infrastructure and resources, improved human capacity and better administrative processes and initiatives for collaboration. CONCLUSION AND RECOMMENDATIONS: The study found that the identified characteristics/features are of high importance either to hurdle or enable the practice of translating animal research into human trials. The study suggests that there should be adequate infrastructure and finance, human capacity building, good research governance, improved ethical and regulatory approval process, multidisciplinary collaboration, and incentives and recognition for researchers to overcome the identified challenges and allow translating of animal research into human trials to proceed more efficiently.

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BACKGROUND: The change in symptoms necessary to be clinically relevant in obsessive-compulsive disorder (OCD) is currently unknown. In this study, we aimed to create an empirically validated threshold for clinical significance or minimal important difference (MID). METHODS: We analyzed individual participant data from short-term, double-blind, placebo-controlled registration trials of selective serotonin reuptake inhibitors in adult OCD patients. Data were collected from baseline to week 12. We used equipercentile linking to equate changes in the Clinical Global Impression (CGI) scale to changes in the Yale-Brown Obsessive-Compulsive Scale (YBOCS). We defined the MID as the YBOCS change linked to a CGI improvement of 3 (defined as "minimal improvement"). RESULTS: We included 7 trials with a total of 1216 patients. The CGI-scores and YBOCS were moderately to highly correlated. The MID corresponded to 4.9 YBOCS points (95% CI 4.4-5.4) for the full sample, or a 24% YBOCS-decrease compared to baseline. The MID varied with baseline severity, being lower in the group with mild symptoms and higher in the group with severe symptoms. CONCLUSIONS: By linking the YBOCS to the CGI-I, this is the first study to propose an MID in OCD trials. Having a clearly defined MID can guide future clinical research and help interpretation of efficacy of existing interventions. Our results are clinician-based; however, there is further need for patient-reported outcomes as anchor to the YBOCS.

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AIM: This is a report of the 5-year results of a two-group parallel randomized clinical trial comparing longitudinal implant stability, and clinical and radiographic peri-implant outcomes of mandibular overdentures retained by one (1-IOD group) or two (2-IOD group) implants. METHODS: All participants received 4.1 mm diameter tissue-level implants (Straumann® Standard Plus - SLActive®, Institut Straumann AG), installed in the mandible midline (1-IOD; n = 23) or the lateral incisor-canine area bilaterally (2-IOD; n = 24), and loaded after 3 weeks. Implant Stability Quotient (ISQ) was measured using a resonance frequency device (Osstell® Mentor, Integration Diagnostics) at implant placement, after three weeks (loading), and at the 6-month, 1-, 3-, and 5-year follow-ups. Marginal bone loss and clinical implant outcomes (plaque, calculus, suppuration and bleeding) were assessed periodically up to 5 years after loading. RESULTS: Only minor changes in marginal bone level were observed after 5 years (mean = 0.37; SD = 0.44 mm), and satisfactory and stable peri-implant parameters were observed throughout the 5-year follow-up. No significant differences between groups were found. Overall, the mean primary implant stability was considered high (> 70) for the two groups (1-IOD = 78.1 ± 4.5; 2-IOD = 78.0 ± 5.8). No noticeable changes were observed between implant insertion and loading. A marked increase was observed from insertion to the 6-month follow-up - the mean difference for the 1-IOD group was + 5.5 ± 5.5 (Effect size = 1.00), while for the 2-IOD group, the mean difference was + 6.0 ± 5.6 (Effect size = 1.08). No relevant changes were observed throughout the follow-up periods up to 5 years. Linear mixed-effect model regression showed no influence of the bone-related variables (p > 0.05) and the number of implants (p = 0.087), and a significant effect of the time variable (p < 0.001). CONCLUSION: Satisfactory peri-implant outcomes and stable secondary stability suggest good clinical performance and successful long-term osseointegration of the implants for single and two-implant mandibular overdentures. Using a single implant to retain a mandibular overdenture does not seem to result in detrimental implant loading over the five years of overdenture use. CLINICAL RELEVANCE: This study corroborates the use of a single implant to retain a mandibular denture.

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This systematic review evaluates the efficacy of rituximab in inducing and maintaining remission in patients with granulomatosis with polyangiitis (GPA). We conducted a comprehensive search across multiple databases, identifying 81 studies, of which 11 met our inclusion criteria after rigorous screening and assessment for relevance and quality. Our analysis shows that rituximab, compared to traditional treatments such as cyclophosphamide and azathioprine, significantly improves remission rates and reduces relapse frequency in GPA patients. Notably, rituximab's benefits extend across various patient demographics, including pediatric groups, and are evident in different dosing regimens, highlighting its versatility and potential as a first-line therapy. The review also underscores the importance of personalized medicine approaches in managing GPA, as rituximab's effectiveness was particularly pronounced in patients with relapsing disease forms. Future research should focus on long-term outcomes, optimal dosing strategies, and the economic implications of widespread rituximab use in clinical practice. Our findings advocate for the integration of rituximab into standard treatment protocols for GPA, offering new hope for patients afflicted with this challenging autoimmune disorder.

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Gastric cancer (GC) poses a significant global health challenge, ranking fifth in incidence and third in mortality among all malignancies worldwide. Its insidious onset, aggressive growth, proclivity for metastasis, and limited treatment options have contributed to its high fatality rate. Traditional approaches for GC treatment primarily involve surgery and chemotherapy. However, there is growing interest in targeted therapies and immunotherapies. This comprehensive review highlights recent advancements in GC targeted therapy and immunotherapy. It delves into the mechanisms of various strategies, underscoring their potential in GC treatment. Additionally, the review evaluates the efficacy and safety of relevant clinical trials. Despite the benefits observed in numerous advanced GC patients with targeted therapies and immunotherapies, challenges persist. We discuss pertinent strategies to overcome these challenges, thereby providing a solid foundation for enhancing the clinical effectiveness of targeted therapies and immunotherapies.

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Chronic migraine is a debilitating headache disorder that is associated with excessive analgesic use. As the long-term use of analgesics could cause additional headaches due to medication overuse, there is a need to probe efficient nonprophylactic alternatives and migraineurs' long-term adherence to such possible treatments. This protocol investigates the integration of neurofeedback and mindfulness which are the two common nonpharmacological therapies for migraines. We offer the use of portable EEG headbands for easy home-based data collection and consistent data access from researchers. In order to evaluate the efficacy of this recommended intervention, this is a protocol for a randomized control trial with a waitlisted group and an intervention group consisting of a daily attention task. The protocol presents important criteria which should be checked for consistency in longitudinal data collection from adults with chronic migraine.

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This review delves into the generation and therapeutic applications of mesenchymal stem cell-derived neural progenitors (MSC-NPs) in Multiple Sclerosis (MS), a chronic autoimmune disease characterized by demyelination, neuroinflammation, and progressive neurological dysfunction. Most current treatment paradigms primarily aimed at regulating the immune response show little success against the neurodegenerative aspect of MS. This calls for new therapies that would play a role in neurodegeneration and functional recovery of the central nervous system (CNS). While utilizing MSC was found to be a promising approach in MS therapy, the initiation of MSC-NPs therapy is an innovation that introduces a new perspective, a dual-action plan, that targets both the immune and neurodegenerative mechanisms of MS. The first preclinical studies using animal models of the disease showed that MSC-NPs could migrate to damaged sites, support remyelination, and possess immunomodulatory properties, thus, providing a solid basis for their human application. Based on pilot feasibility studies and phase I clinical trials, this review covers the transition from preclinical to clinical phases, where intrathecally administered autologous MSC-NPs has shown great hope in treating patients with progressive MS by providing safety, tolerability, and preliminary efficacy. This review, after addressing the role of MSCs in MS and its animal model of experimental autoimmune encephalomyelitis (EAE), highlights the significance of the MSC-NP therapy by organizing its advancement processes from experimental models to clinical translation in MS treatment. It points out the continuing obstacles, which require more studies to improve therapeutic protocols, uncovers the mechanisms of action, and establishes long-term efficacy and safety in larger controlled trials.

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Hydrogels are biomolecules made of artificial and natural polymers. Their quasi-three-dimensional structure has created unique features. They are very hydrophilic, and in addition to the high inflation rate, they also have excellent water maintenance capacity, biodegradability, biocompatibility, and strong mechanical properties. These properties are used in many tissue engineering applications. All these features have made these scaffolds widely used as attractive structures in the world of tissue engineering and regeneration medicine. In addition to research, scaffolds entered the field of medicine and are expected to play a significant role in the repair of many tissues in the future. This study aims to review the various polymers involved in hydrogel fabrication and their application in the repair of diverse tissues and clinical trials.

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Purpose: This study aims to conduct a network meta-analysis to compare the clinical efficacy of seven distinct non-pharmacological therapies for knee osteoarthritis. We hope that our research findings can provide reference for clinical practitioners in formulating treatment plans. Methods: Through a computer-based search, we systematically retrieved randomized controlled trials (RCTs) on non-pharmacological therapies for knee osteoarthritis from eight databases, including CNKI, Wanfang, VIP, PubMed, Web of Science, Embase, Scopus, and The Cochrane Library. Following screening, data extraction, and methodological quality assessment, relevant data were included and analyzed using R 4.2.3 software. Results: A comprehensive analysis of 24 RCTs involving 2582 patients encompassed seven diverse non-pharmacological therapies. The efficacy rankings, based on Visual Analog Scale (VAS) scores, were as follows: shock wave therapy > needle-knife > laser therapy > acupuncture > ultrasound > exercise > transcutaneous electrical nerve stimulation. Similarly, based on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores, the efficacy rankings were as follows: shock wave therapy > needle-knife > laser therapy > acupuncture > ultrasound > transcutaneous electrical nerve stimulation > exercise. Among the three WOMAC subscales, the efficacy rankings for non-pharmacological therapies were as follows: For stiffness: laser therapy > exercise > shock wave therapy > acupuncture > needle-knife > ultrasound > transcutaneous electrical nerve stimulation; For daily activities: shock wave therapy > laser therapy > needle-knife > acupuncture > ultrasound > transcutaneous electrical nerve stimulation > exercise; For pain: shock wave therapy > needle-knife > laser therapy > acupuncture > exercise > transcutaneous electrical nerve stimulation > ultrasound. Conclusion: Based on the currently limited research, we can prioritize the use of shockwave therapy to treat patients with knee osteoarthritis. However, it is essential to emphasize that further rigorous and well-designed randomized controlled trials are necessary to validate the conclusions drawn from this study.

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The CIOMS book "International Ethical Guidelines for Health-related Research Involving Humans", published in 2016 (IEG2016), provides information to assist research ethics committee members and research practitioners with pragmatically implementing ethical considerations while planning and conducting their research. To identify which aspects of research IEG2016 has had the greatest impact since its publication, we analyzed metadata from 942 papers that cited IEG2016 (English language title only) from Web of Science (WoS, Clarivate). Using VOSviewer, we mapped the co-occurrence of keywords to derive the network of all keywords that co-occurred at least five times in the set of citing papers. We found that the keywords ethics, research ethics, informed consent, and clinical trials had high co-occurrence scores in this set of publications. Strong links were also observed between ethics, research ethics, and informed consent. We identified fifteen human-related (HR) keyword nodes in this keyword network. Analysis of the subset of 273 IEG2016-citing articles containing these fifteen HR keywords showed later-date publications were focused on the youngest humans (children, adolescents, young people, minors) and the humans typically responsible for those youngest humans, namely women and parents. Seventy-nine of the 110 networked countries/regions associated with IEG2016-citing articles were home to HR keyword articles. We conclude that IEG2016 has had significant impact in health and medical science literature and has served as a foundation for health-related research around the world in the areas of ethics, informed consent, and research ethics and the linkage of these topics to under-represented populations in such research.

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Gene therapy as a disease-modifying therapeutic approach for neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), is a promising avenue. Promising results in the preclinical studies involving rodents and nonhuman primates utilizing gene therapy have led to multiple clinical trials evaluating various genes of interest for AD and PD. In AD, clinical trials are assessing gene therapy involving brain-derived neurotrophic factor (BDNF) and other targets such as apolipoprotein E2 (APOE2) and human telomerase reverse transcriptase (hTERT). In PD, clinical trials are evaluating gene therapy delivering neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF). Additionally, gene therapy delivering enzymes aromatic L-amino acid decarboxylase (AADC) and glutamic acid decarboxylase (GAD) are also being evaluated for PD. All these trials primarily utilized adeno-associated virus (AAV) to deliver the above transgene of interest. This review summarizes the current clinical trials involving gene therapy for AD and PD. It also discusses the challenges and opportunities associated with the gene therapy approach in AD and PD and ongoing developments related to increasing the safety and efficacy of the gene therapy for long-term outcomes, which include evaluation of various serotypes and administration routes. This comprehensive review emphasizes translating preclinical findings into clinical trials, further directions, and the potential for this promising therapeutic approach to alleviate neurodegenerative disease.

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Background: Hereditary transthyretin (ATTRv) amyloidosis, a multifaceted disorder affecting multiple systems, substantially diminishes patients' physical capabilities and overall quality of life. Patisiran and Vutrisiran, two Ribonucleic acid (RNA) interference therapies, target reducing both pathogenic and wild-type transthyretin (TTR) protein levels. This systematic review assesses the effectiveness and safety of these treatments in managing ATTRv. Methods: A comprehensive, thorough literature search across databases including Embase, PubMed, Web of Science, Cochrane Central, and Google Scholar yielded 858 studies. Following removing duplicate and irrelevant articles, 676 distinct studies underwent review. These studies, conducted on a global scale, encompassed a range of methodologies, including clinical trials and indirect treatment comparisons. Results: Ten studies, spanning a total population of 756 patients, were selected for in-depth analysis. Patisiran and Vutrisiran consistently demonstrated significant improvements in primary and secondary endpoints related to neuropathy, quality of life, and cardiac function. Both medications were well-tolerated, with primarily mild to moderate adverse events. Indirect treatment comparison studies indicated Vutrisiran's superiority over Tafamidis in treating ATTRv amyloidosis. Conclusion: This systematic review recommends using Patisiran and Vutrisiran to treat ATTRv amyloidosis. The findings suggest that these RNA interference therapies improve neuropathy, quality of life, and cardiac symptoms. The results indicate sustained benefits over prolonged treatment, with satisfactory safety profiles. However, potential biases, conflicts of interest in the studies, and limited follow-up periods in some trials necessitate cautious interpretation. Future research should address these limitations and provide more robust evidence for the long-term efficacy and safety of Patisiran and Vutrisiran in ATTRv treatment.

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BACKGROUNDFrailty significantly affects morbidity and mortality rates in the older population (age >65 years). Age-related degenerative diseases are influenced by the intestinal microbiota. However, limited research exists on alterations in the intestinal microbiota in frail older individuals, and the effectiveness of prebiotic intervention for treating frailty remains uncertain.OBJECTIVEWe sought to examine the biological characteristics of the intestinal microbiome in frail older individuals and assess changes in both frailty status and gut microbiota following intervention with a prebiotic blend consisting of inulin and oligofructose.METHODSThe study consisted of 3 components: an observational analysis with a sample size of 1,693, a cross-sectional analysis (n = 300), and a multicenter double-blind, randomized, placebo-controlled trial (n = 200). Body composition, commonly used scales, biochemical markers, intestinal microbiota, and metabolites were examined in 3 groups of older individuals (nonfrail, prefrail, and frail). Subsequently, changes in these indicators were reevaluated after a 3-month intervention using the prebiotic mixture for the prefrail and frail groups.RESULTSThe intervention utilizing a combination of prebiotics significantly improved frailty and renal function among the older population, leading to notable increases in protein levels, body fat percentage, walking speed, and grip strength. Additionally, it stimulated an elevation in gut probiotic count and induced alterations in microbial metabolite expression levels as well as corresponding metabolic pathways.CONCLUSIONSThe findings suggest a potential link between changes in the gut microbiota and frailty in older adults. Prebiotics have the potential to modify the gut microbiota and metabolome, resulting in improved frailty status and prevention of its occurrence.TRIAL REGISTRATIONClinicalTrials.gov NCT03995342.

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Background: Results from clinical trials investigating the effect of nuts consumption on cognition are conflicting. We decided to conduct the current meta-analysis to summarize all available evidence on the effect of consuming nuts on cognition scores. Methods: We conducted a comprehensive search in the online databases using relevant keywords up to June 2024. We included all the published Randomized clinical trials (RCTs) investigating the effect of nuts, compared to control, on cognition scores. Results: Overall, 5 trials were included with a total sample size of 928 adults. Based on 6 effect sizes from these 5 trials, we did not find a significant effect of nuts on cognition function [Standardized Mean Difference (SMD): 0.27, 95% CI: -0.65 to 1.19, p = 0.57]. Conclusion: Our review could not find a significant effect of nuts on cognition function. Future high-quality RCTs with larger sample sizes should be conducted to shed light on the impact of nuts on cognition.

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Introduction: Anthropometric measurements provide valuable information about infant growth patterns and can help identify nutrition, growth, and developmental concerns. With the increasing use of telehealth and decentralized clinical trial approaches, there is potential for caregivers to collect anthropometric measurements at home via teleconference with healthcare providers (HCPs) to monitor infant growth, which indirectly reflects health status. This study aimed to evaluate whether telehealth-guided caregivers can utilize standardized methods and home-use measurement equipment to collect reliable anthropometric measurements compared to HCPs and study nurses. Methods: The study compared the weight, length, and head circumference measurements collected by caregivers (n = 8 pairs), pediatric HCPs (n = 7), and study nurses (n = 4), who served as the gold standard comparator group. Four silicone dolls with varied anthropometrics were used as surrogates for human infants. Results: Caregiver inter- and intra-observer technical errors of measurement (TEMs) were all equal to or below the maximum allowed error (MAE). For HCPs, only intra-observer TEM for length and inter-observer TEM for HC and length were within the MAE. There was no evidence of bias for either caregiver or HCP measurements compared to the gold standard. Coefficients of reliability (R) were greater than 0.96 for all measurements. Discussion: Preliminary results from this study demonstrate that telehealth-guided caregivers can capture accurate and reliable anthropometric measurements compared to HCPs. The results suggest that remote measurement collection allows for more frequent monitoring while reducing the burden on patients and caregivers in primary care and clinical trials such as infant formula growth monitoring studies.

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Objective: The COVID-19 pandemic led to immediate changes in cancer clinical trial conduct. The primary aims of this study were to summarize the impact of the pandemic on Alliance for Clinical Trials in Oncology (Alliance) enrollment, protocol deviations, COVID-19 events (positive or presumptive-positive COVID test), and premature study discontinuation rates. Methods: Enrollment trends were examined from January 2019 (pre COVID-19 pandemic) through 2022. Data were captured for protocol deviations and premature treatment and study discontinuation events across all Alliance protocols using a centralized Medidata Rave database, and summarized from January 1, 2020, through June 30, 2022. Descriptive statistics and graphical techniques are used to summarize observed trends. Results: Overall enrollment across Alliance trials decreased during the COVID-19 pandemic and remained below pre-pandemic levels in 2022. Racial and ethnic demographics of enrolled patients did not change substantially. 4805 protocol deviations were reported on 2745 unique patients, with at least one protocol deviation reported by 618 sites and 77 unique trials. Commonly reported deviations were telemedicine visits (n=2167, 45%) and late/missed study procedures (n=2150, 45%). A total of 826 COVID-19 events were reported in 659 unique patients. Of an estimated 18,000 enrolled patients, only 68 withdrew from treatment and 45 withdrew from study due to COVID-19. Conclusion: A centralized COVID-19 database enabled a comprehensive assessment of the impact of the pandemic across Alliance trials. COVID-19 led to an immediate decline in enrollment across all patient populations. While the number of trials open to patient accrual remained stable, several large, adjuvant studies completed accrual during this period, which contributed to accrual decline. Telemedicine usage was notable, and both COVID-19 events and study discontinuation due to COVID-19 were rare.