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The usual challenges of conducting primary care research, including randomized trials, have been exacerbated, and new ones identified, during the COVID-19 pandemic. HOMER (Home versus Office for Medication Enhanced Recovery; subsequently, Comparing Home, Office, and Telehealth Induction for Medication Enhanced Recovery) is a pragmatic, comparative-effectiveness research trial that aims to answer a key question from patients and clinicians: What is the best setting in which to start treatment with buprenorphine for opioid use disorder for this patient at this time? In this article, we describe the difficult journey to find the answer. The HOMER study began as a randomized trial comparing treatment outcomes in patients starting treatment with buprenorphine via induction at home (unobserved) vs in the office (observed, synchronous). The study aimed to enroll 1,000 participants from 100 diverse primary care practices associated with the State Networks of Colorado Ambulatory Practices and Partners and the American Academy of Family Physicians National Research Network. The research team faced unexpected challenges related to the COVID-19 pandemic and dramatic changes in the opioid epidemic. These challenges required changes to the study design, protocol, recruitment intensity, and funding conversations, as well as patience. As this is a participatory research study, we sought, documented, and responded to practice and patient requests for adaptations. Changes included adding a third study arm using telehealth induction (observed via telephone or video, synchronous) and switching to a comprehensive cohort design to answer meaningful patient-centered research questions. Using a narrative approach based on the Greek myth of Homer, we describe here the challenges and adaptations that have provided the opportunity for HOMER to thrive and find the way home. These clinical trial strategies may apply to other studies faced with similar cultural and extreme circumstances. [ABSTRACT FROM AUTHOR]

Background: Public involvement enhances the relevance, quality, and impact of research. There is some evidence that public involvement in Australian research lags other countries, such as the United Kingdom. The purpose of the systematic review was to establish the rates and describe the characteristics of public involvement in Australian clinical trials. Methods: We reviewed evidence of public involvement in all Australian randomised controlled trials published in the first 6 months of 2021. To determine the quality of public involvement, we used the five-item short-form version of the Guidance of Reporting Involvement Patients and the Public, version 2. Results: In total, 325 randomised controlled trials were included, of which 17 (5%) reported any public involvement. Six trials reported public involvement in setting the research aim and seven in developing study methods. The authors of one study reflected on the overall role and influence of public involvement in the research. Conclusion: Rate of public involvement in Australian clinical trials is seemingly substantially lower than those reported in countries with similar advanced public health care systems, notably the United Kingdom. Our observations may be explained by a lack of researcher skills in how to involve the public and the failure by major funding agencies in Australia to mandate public involvement when deciding on how to award grant funding. [ABSTRACT FROM AUTHOR]

This article explores the benefits and risks of anti-amyloid therapy for individuals with Alzheimer's disease. It focuses on the development of new monoclonal antibodies that target amyloid-β and their potential to slow down the progression of the disease. Clinical trial data is presented, demonstrating the effectiveness of these antibodies in reducing amyloid-β levels, although the clinical benefits in terms of cognitive decline are modest. The article also addresses the challenges of communicating this information to patients and caregivers, as well as the importance of personalized assessments when considering the benefits and risks of anti-amyloid therapy. It concludes by acknowledging the risks involved but also highlighting the promising advancements in this field and the ongoing search for effective and safe treatments for Alzheimer's disease. [Extracted from the article]

We summarize the clinical trials (CTs) main characteristics, including members of ethnic minorities from Latin America. We carried out a systematic search in six databases. We made a descriptive synthesis of CTs, summarizing the characteristics, interventions, main findings, results, and conclusions reported. 4411 studies were acquired in search strategy, leaving 24 CTs in the final selection. Of these, ten were randomized, four were non-randomized, and the remainder had other designs. Most of the studies were carried out in the population of infants and children (08), ten of the studies included only women, and two studies included men. Nine studies were conducted in Mexico, with the Mayan ethnic minority being mostly evaluated (05). In only 15 it was mentioned that their research was approved by a research ethics committee. Finally, half of the CTs reported funding from international agencies and third reported funding from government agencies. Our results show that that CTs in ethnic minorities are limited and reduced to a few native peoples of the continent. [ABSTRACT FROM AUTHOR]

Abstract Objectives Despite the significant disease burden due to cardiac arrest, there is a relative paucity of randomized controlled trials (RCTs) to inform definitive management. We aimed to evaluate the current scope of cardiac arrest RCTs published between 2015 and 2022. Methods We conducted a search in October 2023 of MEDLINE, Embase, and Web of Science for cardiac arrest RCTs. We included trials published between 2015 and 2022 enrolling human subjects suffering from non‐traumatic cardiac arrest. Descriptive statistics were reported and the Mann Kendall test was used to evaluate for temporal trends in the number of trials published annually. Results We identified 1764 unique publications, 87 RCTs were included after title/abstract and full‐text review. We found no significant increase in trials published annually (eight in 2015 and 16 in 2022, p = 1.0). Geographic analysis of study centers found 31 countries represented; Denmark (n = 13, 15%) and the United States (n = 9, 10%) conducted the majority of trials. Nearly all trials included adults (n = 84, 97%) and few included children (n = 9, 10%). The majority of trials focused on out‐of‐hospital cardiac arrest (n = 62, 71%). Thirty‐eight (44%) trials used an intervention characterized as a process improvement; 28 (32%) interventions were characterized as a drug and 20 (23%) as a device. Interventions were implemented with similar frequency in the prehospital (33%) and intensive care unit (38%) setting, as well as similarly between the intra‐arrest (53%) and post‐arrest (46%) periods. Twenty (27%) trials selected a primary outcome of survival at ≥ 28 days. Conclusions Publication of cardiac arrest RCTs remained constant between 2015 and 2022. We identified significant gaps including a lack of trials examining in‐hospital cardiac arrest and pediatric patients.

In their recent Viewpoint article, Beidas et al. (2023) argue that researchers should test psychosocial interventions in the contexts in which they are meant to be delivered and that they can accelerate the deployment of these interventions by advancing directly from pilot trials to effectiveness and implementation studies without conducting efficacy trials. In this commentary, we argue that this is a well-intended but problematic approach and that there is a more productive strategy for translational behavioral intervention research. The commentary discusses issues concerning intervention development, refinement, and optimization; pilot and efficacy testing of interventions; the contexts in which interventions are delivered; clinical practice guidelines; and quick versus programmatic answers to significant clinical research questions. Testing psychosocial interventions in the contexts in which they are meant to be delivered is a complex task for interventions that are designed to be used in a wide variety of contexts. Nevertheless, interventions can be tested in the contexts in which they are meant to be delivered without sacrificing programmatic intervention development or safety and efficacy testing. What is the public health significance of this article?: Safe and effective psychosocial interventions are needed for a wide variety of clinical or public health problems. The best way for researchers to meet these needs is to conduct studies to ensure that their interventions are safe and effective before deploying them in public health or clinical service settings. [ABSTRACT FROM AUTHOR]

To gain a comprehensive overview of the landscape of clinical trials for the H1-receptor antagonists (H1R antagonists) cetirizine, levocetirizine, loratadine, desloratadine, and fexofenadine and their potential use cases in drug repurposing (the use of well-known drugs outside the scope of the original medical indication), we analyzed trials from clincialtrials.gov using novel custom-coded software, which itself is also a key emphasis of this paper. To automate data acquisition from clincialtrials.gov via its API, data processing, and storage, we created custom software by leveraging a variety of open-source tools. Data were stored in a relational database and annotated facilitating a specially adapted web application. Through the data analysis, we identified use cases for repurposing and reviewed backgrounds and results in the scientific literature. Even though we found very few trials with published results for repurpose indications, extended literature research revealed some prominent use cases: Cetirizine seems promising in mitigating infusion-associated reactions and is also more effective than placebo in the treatment of androgenetic alopecia. Loratadine may be beneficial in the prophylaxis of G-CSF-related bone pain. In COVID-19, H1R antagonists may be helpful, but placebo-controlled scientific evidence is needed. For asthma, the effect of H1R antagonists only seems to be secondary by alleviating allergy symptoms. Our novel method to find potential use cases for repurposing of H1R antagonists allows for high automation, reduces human error, and was successful in revealing potential areas of interest. The software could be used for similar research questions and analyses in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND: Atrial fibrillation (AF) is common in patients undergoing transcatheter aortic valve replacement (TAVR) and is associated with increased risk of bleeding and stroke. While left atrial appendage occlusion (LAAO) is approved as an alternative to anticoagulants for stroke prevention in patients with AF, placement of these devices in patients with severe aortic stenosis, or when performed at the same time as TAVR, has not been extensively studied. METHODS: WATCH-TAVR (WATCHMAN for Patients with AF Undergoing TAVR) was a multicenter, randomized trial evaluating the safety and effectiveness of concomitant TAVR and LAAO with WATCHMAN in AF patients. Patients were randomized 1:1 to TAVR + LAAO or TAVR + medical therapy. WATCHMAN patients received anticoagulation for 45 days followed by dual antiplatelet therapy until 6 months. Anticoagulation was per treating physician preference for patients randomized to TAVR + medical therapy. The primary noninferiority end point was all-cause mortality, stroke, and major bleeding at 2 years between the 2 strategies. RESULTS: The study enrolled 349 patients (177 TAVR + LAAO and 172 TAVR + medical therapy) between December 2017 and November 2020 at 34 US centers. The mean age of patients was 81 years, and the mean scores for CHA2DS2-VASc and HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly) were 4.9 and 3.0, respectively. At baseline, 85.4% of patients were taking anticoagulants and 71.3% patients were on antiplatelet therapy. The cohorts were well-balanced for baseline characteristics. The incremental LAAO procedure time was 38 minutes, and the median contrast volume used for combined procedures was 119 mL versus 70 mL with TAVR alone. At the 24-month follow-up, 82.5% compared with 50.8% of patients were on any antiplatelet therapy, and 13.9% compared with 66.7% of patients were on any anticoagulation therapy in TAVR + LAAO compared with TAVR + medical therapy group, respectively. For the composite primary end point, TAVR + LAAO was noninferior to TAVR + medical therapy (22.7 versus 27.3 events per 100 patient-years for TAVR + LAAO and TAVR + medical therapy, respectively; hazard ratio, 0.86 [95% CI, 0.60-1.22]; Pnoninferiority<0.001). CONCLUSIONS: Concomitant WATCHMAN LAAO and TAVR is noninferior to TAVR with medical therapy in severe aortic stenosis patients with AF. The increased complexity and risks of the combined procedure should be considered when concomitant LAAO is viewed as an alternative to medical therapy for patients with AF undergoing TAVR. [ABSTRACT FROM AUTHOR]

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This article discusses the importance of increasing access to new therapies for Australian children and adolescents through clinical trials. It emphasizes the need for investment and a coordinated national approach to ensure that Australian children do not fall behind their international peers. The article highlights the benefits of collaborative approaches and strategic investment in pediatric clinical trials, as well as the challenges in delivering high-quality trials in this population. It acknowledges the additional challenges faced in Australia due to distance and regulatory factors, and calls for equitable access to emerging treatments for all Australian children, regardless of their circumstances. The article concludes by emphasizing the need for national investment in pediatric clinical trial delivery in Australia. [Extracted from the article]

BACKGROUND: Among patients treated with statin therapy to guideline-recommended cholesterol levels, residual inflammatory risk assessed by high-sensitivity C-reactive protein (hsCRP) is at least as strong a predictor of future cardiovascular events as is residual risk assessed by low-density lipoprotein cholesterol (LDLC). Whether these relationships are present among statin-intolerant patients with higher LDLC levels is uncertain but has implications for the choice of preventive therapies, including bempedoic acid, an agent that reduces both LDLC and hsCRP. METHODS: The multinational CLEAR-Outcomes trial (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen Outcomes Trial) randomly allocated 13 970 statin-intolerant patients to 180 mg of oral bempedoic acid daily or matching placebo and followed them for a 4-component composite of incident myocardial infarction, stroke, coronary revascularization, or cardiovascular death, and for all-cause mortality. Quartiles of increasing baseline hsCRP and LDLC were assessed as predictors of future adverse events after adjustment for traditional risk factors and randomized treatment assignment. RESULTS: Compared with placebo, bempedoic acid reduced median hsCRP by 21.6% and mean LDLC levels by 21.1% at 6 months. Baseline hsCRP was significantly associated with the primary composite end point of major cardiovascular events (highest versus lowest hsCRP quartile; hazard ratio [HR], 1.43 [95% CI, 1.24-1.65]), cardiovascular mortality (HR, 2.00 [95% CI, 1.53-2.61]), and all-cause mortality (HR, 2.21 [95% CI, 1.79-2.73]). By contrast, the relationship of baseline LDLC quartile (highest versus lowest) to future events was smaller in magnitude for the primary composite cardiovascular end point (HR, 1.19 [95% CI, 1.04-1.37]) and neutral for cardiovascular mortality (HR, 0.90 [95% CI, 0.70-1.17]) and all-cause mortality (HR, 0.95 [95% CI, 0.78-1.16]). Risks were high for those with elevated hsCRP irrespective of LDLC level. Bempedoic acid demonstrated similar efficacy in reducing cardiovascular events across all levels of hsCRP and LDLC. CONCLUSIONS: Among contemporary statin-intolerant patients, inflammation assessed by hsCRP predicted risk for future cardiovascular events and death more strongly than hyperlipidemia assessed by LDLC. Compared with placebo, bempedoic acid had similar efficacy for reducing cardiovascular risk across hsCRP and LDLC strata. [ABSTRACT FROM AUTHOR]

Background: Data monitoring committees advise on clinical trial conduct through appraisal of emerging data to ensure participant safety and scientific integrity. While consideration of their use is recommended for trials performed with vulnerable populations, previous research has shown that data monitoring committees are reported infrequently in publications of pediatric randomized controlled trials. We aimed to assess the frequency of reported data monitoring committee adoption in ClinicalTrials.gov registry records and to examine the influence of key trial characteristics. Methods: We conducted a cross-sectional data analysis of all randomized controlled trials performed exclusively in a pediatric population and registered in ClinicalTrials.gov between 2008 and 2021. We used the Access to Aggregate Content of ClinicalTrials.gov database to retrieve publicly available information on trial characteristics and data on safety results. Abstracted data included reported trial design and conduct parameters, population and intervention characteristics, reasons for prematurely halting, serious adverse events, and mortality outcomes. We performed descriptive analyses on the collected data and explored the influence of clinical, methodological, and operational trial characteristics on the reported adoption of data monitoring committees. Results: We identified 13,928 pediatric randomized controlled trial records, of which 39.7% reported adopting a data monitoring committee, 49.0% reported not adopting a data monitoring committee, and 11.3% did not answer on this item. While the number of registered pediatric trials has been increasing since 2008, we found no clear time trend in the reported adoption of data monitoring committees. Data monitoring committees were more common in multicenter trials (50.6% vs 36.9% for single-center), multinational trials (60.2% vs 38.7% for single-country), National Institutes of Health–funded (60.3% vs 40.1% for industry-funded or 37.5% for other funders), and placebo-controlled (47.6% vs 37.5% for other types of control groups). Data monitoring committees were also more common among trials enrolling younger participants, trials employing blinding techniques, and larger trials. Data monitoring committees were more common in trials with at least one serious adverse event (52.6% vs 38.4% for those without) as well as for trials with reported deaths (70.3% vs 38.9% for trials without reported deaths). In all, 4.9% were listed as halted prematurely, most often due to low accrual rates. Trials with a data monitoring committee were more often halted for reasons related to scientific data than trials without a data monitoring committee (15.7% vs 7.3%). Conclusion: According to registry records, the use of data monitoring committees in pediatric randomized controlled trials was more frequent than previously reported in reviews of published trial reports. The use of data monitoring committees varied across key clinical and trial characteristics based on which their use is recommended. Data monitoring committees may still be underutilized in pediatric trials, and reporting of this item could be improved. [ABSTRACT FROM AUTHOR]

Background: Robust evidence regarding the benefits and harms of notifying Australian women when routine breast screening identifies that they have dense breasts is needed for informing future mammography population screening practice and policy. Objectives: To assess the psychosocial and health services use effects of notifying women participating in population‐based breast cancer screening that they have dense breasts; to examine whether the mode of communicating this information about its implications (print, online formats) influences these effects. Methods and analysis: The study population comprises women aged 40 years or older who attend BreastScreen Queensland Sunshine Coast services for mammographic screening and are found to have dense breasts (BI‐RADS density C or D). The randomised controlled trial includes three arms (952 women each): standard BreastScreen care (no notification of breast density; control arm); notification of dense breasts in screening results letter and print health literacy‐sensitive information (intervention arm 1) or a link or QR code to online video‐based health literacy‐sensitive information (intervention arm 2). Baseline demographic data will be obtained from BreastScreen Queensland. Outcomes data will be collected in questionnaires at baseline and eight weeks, twelve months, and 27 months after breast screening. Primary outcomes will be psychological outcomes and health service use; secondary outcomes will be supplemental screening outcomes, cancer worry, perceived breast cancer risk, knowledge about breast density, future mammographic screening intentions, and acceptability of notification about dense breasts. Ethics approval: Gold Coast Hospital and Health Service Ethics Committee (HREC/2023/QGC/89770); Sunshine Coast Hospital and Health Service Research Governance and Development (SSA/2023/QSC/89770). Dissemination of findings: Findings will be reported in peer‐reviewed journals and at national and international conferences. They will also be reported to BreastScreen Queensland, BreastScreen Australia, Cancer Australia, and other bodies involved in cancer care and screening, including patient and support organisations. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12623000001695p (prospective: 9 January 2023). [ABSTRACT FROM AUTHOR]

Clinical research is essential to modern evidence-based medicine. The potential for human harm must be minimized and balanced against the greater utility to society. With a multitude of clinical, governmental, and regulatory actors now working to ensure clinical research is ethically robust, it is important that we reflect on the current paradigm of clinical research in the UK, to safeguard participant safety. We also discuss ethical principles of clinical trials, according to different bioethical models. [ABSTRACT FROM AUTHOR]

Simple Summary: This study assessed the feasibility of surgical trial comparing neck dissection procedures with and without fibrin sealant and whether the proposed trial design was effective. It demonstrated the benefits of pilot/feasibility work prior to a definitive trial. The study concluded that primary outcomes in Head & Neck surgical trials benefit from being pragmatic. Furthermore, research sites without established trials infrastructure require more time to open. Surgeon credentialling is a vital quality assurance step in most surgical trial designs. Fibrin Sealant improved most clinical outcomes assessed but the signal was weak. Therefore, a decision was made not to progress to the definitive trial. Objectives: High-quality randomised controlled trials (RCT) to support the use of Fibrin Sealants (FS) in neck dissection (ND) are lacking. The DEFeND trial assessed critical pilot/feasibility questions and signals from clinical outcomes to inform a future definitive trial. Patients and Methods: The study design piloted was a blinded surgical RCT. All participants underwent unilateral ND for head and neck cancer. Interventional arm: ND with application of FS. Control arm: ND alone. Feasibility outcomes included recruitment, effectiveness of blinding, protocol adherence and evaluating administrative processes. Clinical outcomes included surgical complications (primary outcome), drainage volume, time to drain removal, length of hospital stay, pain and the Neck Dissection Impairment Index. Results: Recruitment completed ahead of time. Fifty-three patients were recruited, and 48 were randomised at a rate of 5.3 patients/month. Blinding of patients, research nurses and outcome assessors was effective. Two protocol deviations occurred. Two patients were lost to follow-up. The mean (SD) Comprehensive Complication Index in the interventional arm was 6.5 (12.8), and it was 9.9 (14.2) in the control arm. The median (IQR) time to drain removal (days) was shorter in the interventional arm (2.67 (2.42, 3.58) vs. 3.40 (2.50, 4.27)). However, this did not translate to a clinically significant reduction in median (IQR) length of hospital stay in days (intervention: 3.48 (2.64, 4.54), control: 3.74 (3.11, 4.62)). Conclusion: The proposed trial design was effective, and a definitive surgical trial is feasible. Whilst there was a tendency for FS to improve clinical outcomes, the effect size did not reach clinical or statistical significance. (ISRCTN99181100). [ABSTRACT FROM AUTHOR]

Drug development in traumatic brain injury (TBI) has been impeded by the complexity and heterogeneity of the disease pathology, as well as limited understanding of the secondary injury cascade that follows the initial trauma. As a result, patients with TBI have an unmet need for effective pharmacological therapies. One promising drug candidate is cyclosporine, a polypeptide traditionally used to achieve immunosuppression in transplant recipients. Cyclosporine inhibits mitochondrial permeability transition, thereby reducing secondary brain injury, and has shown neuroprotective effects in multiple preclinical models of TBI. Moreover, the cyclosporine formulation NeuroSTAT® displayed positive effects on injury biomarker levels in patients with severe TBI enrolled in the Phase Ib/IIa Copenhagen Head Injury Ciclosporin trial (NCT01825044). Future research on neuroprotective compounds such as cyclosporine should take advantage of recent advances in fluid-based biomarkers and neuroimaging to select patients with similar disease pathologies for clinical trials. This would increase statistical power and allow for more accurate assessment of long-term outcomes. [ABSTRACT FROM AUTHOR]

Australian trial activity compares favourably internationally Australia has a highly active trials community, exemplified by the number, breadth and sponsorship of trials (Box 1). Keywords: Clinical trials as topic; Research design; Registries EN Clinical trials as topic Research design Registries 192 196 5 09/05/23 20230904 NES 230904 Examining the clinical trials landscape in Australia is important for governance and to expand knowledge about trial activity to health professionals, the public and funders. We found that these trials have slightly increased over time; from two trials (0.3% of all trials) in 2006 to 16 trials (1% of all trials) in 2019. In this spirit and in line with international standards, trial registries have the capacity for trialists to report results and trial protocols,[20] the latter being critical for interpreting results. [Extracted from the article]

Background: Identifying a meaningful progression metric for Parkinson's disease (PD) that reflects heterogeneity remains a challenge. Objective: To assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones. Methods: Using data from the Parkinson's Progression Markers Initiative (PPMI) de novo PD cohort, we monitored 25 milestones across six domains ("walking and balance"; "motor complications"; "cognition"; "autonomic dysfunction"; "functional dependence"; "activities of daily living"). Milestones were intended to be severe enough to reflect meaningful disability. We assessed the proportion of participants reaching any milestone; evaluated which occurred most frequently; and conducted a time-to-first-event analysis exploring whether baseline characteristics were associated with progression. Results: Half of participants reached at least one milestone within five years. Milestones within the cognitive, functional dependence, and autonomic dysfunction domains were reached most often. Among participants who reached a milestone at an annual follow-up visit and remained active in the study, 82% continued to meet criteria for any milestone at one or more subsequent annual visits and 55% did so at the next annual visit. In multivariable analysis, baseline features predicting faster time to reaching a milestone included age (p < 0.0001), greater MDS-UPDRS total scores (p < 0.0001), higher GDS-15 depression scores (p = 0.0341), lower dopamine transporter binding (p = 0.0043), and lower CSF total α-synuclein levels (p = 0.0030). Symptomatic treatment was not significantly associated with reaching a milestone (p = 0.1639). Conclusion: Clinically relevant milestones occur frequently, even in early PD. Milestones were significantly associated with baseline clinical and biological markers, but not with symptomatic treatment. Further studies are necessary to validate these results, further assess the stability of milestones, and explore translating them into an outcome measure suitable for observational and therapeutic studies. [ABSTRACT FROM AUTHOR]

In comparison, "adaptive" clinical trials allow pre-specified changes to the trial's design or conduct during the study, without compromising the integrity of the trial. MAMS trials can be used for trialling an intervention at a single phase or can seamlessly combine phase 2 treatment selection and phase 3 efficacy testing in one study. Keywords: Clinical trials as topic; Biostatistics EN Clinical trials as topic Biostatistics 451 454 4 06/06/23 20230601 NES 230601 Flexibility of design is not a panacea, but adaptive clinical trial designs offer the potential for more efficient research Randomised controlled trials, when appropriately designed and conducted, can produce robust evidence for the safety and efficacy of health or medical interventions. [Extracted from the article]

ABSTRACT Introduction: We aimed to evaluate the role of remote proctoring during the initial training phases of a robotics curriculum using surgical robot skills simulator exercises. Materials and Methods: Prospective randomized study comprising 36 urology residents and junior staff urologists without previous robotic training. Group 1 (G1) performed exercises without any assistance or support, group 2 (G2) received support from in-person proctor, and group 3 (G3) from a remote proctor through a telementoring system. Qualitative and quantitative analyses were conducted for each exercise and group. Results: The overall score approval rates (OSA) for the different skill exercises were Ring Walk 2 (RW2) 83%, Energy Dissection 2 (ED2) 81%, and Ring Walk 3 (RW3) 14%. RW2 OSA was higher on attempt 3 than on attempt 1 (83.3% vs. 63.9%, p=0.032). ED2 OSA rate was higher in attempt 3 than in attempt 1 (80.6% vs. 52.8%, p=0.002). RW2 OSA was similar among the groups. In ED2, both remote and live assistance were significantly related to upper OSA (G1=47.2%, G2=75.0%, G3=83.3%, p=0.002). RW3 had similar OSA among the groups, which can be explained by the high level of difficulty and low OSA in all the groups. However, in a sensitive quantitative analysis, the mean overall score of the participants in RW3 was higher in both proctored groups (G1=24, G2=57.5, G3=51.5, p=0.042). Conclusion: Robotic performance increased significantly over three attempts for simulation exercises of low, medium, but not high-complexity. Proctoring, either in-person or remotely, has a positive impact on approval performance, particularly in intermediate tasks.

Background Progression-free survival was significantly longer in patients who received avelumab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma (aRCC) in a randomized phase III trial. We report long-term safety and efficacy of avelumab plus axitinib as first-line treatment for patients with aRCC from the JAVELIN Renal 100 phase Ib trial (NCT02493751). Materials and Methods In this open-label, multicenter, phase Ib study, patients with untreated aRCC received avelumab 10 mg/kg every 2 weeks plus axitinib 5 mg twice daily or with axitinib for 7 days followed by avelumab plus axitinib. Safety and efficacy were assessed in all patients receiving at least one dose of avelumab or axitinib. Results Overall, 55 patients were enrolled and treated. Median follow-up was 55.7 months (95% CI, 54.5-58.7). Treatment-related adverse events of any grade or grade ≥3 occurred in 54 (98.2%) and 34 (61.8%) patients, respectively. The confirmed objective response rate was 60.0% (95% CI, 45.9-73.0), including complete response in 10.9% of patients. Median duration of response was 35.9 months (95% CI, 12.7-52.9); the probability of response was 65.8% (95% CI, 46.7-79.4) at 2 years. Median progression-free survival was 8.3 months (95% CI, 5.3-32.0). Median overall survival was not reached (95% CI, 40.8-not estimable); the 5-year overall survival rate was 57.3% (95% CI, 41.2-70.5). Conclusion Five-year follow-up for combination treatment with avelumab plus axitinib in previously untreated patients with aRCC showed long-term clinical activity with no new safety signals, supporting use of this regimen within its approved indication in clinical practice (Clinicaltrials.gov NCT02493751). [ABSTRACT FROM AUTHOR]

The article comments on a study by Andre Pontes-Silva and colleague on the effect of physiological factors on the performance of transgender athletes. Topics mentioned include the assessment of body proportionality, the evaluation of endocrine system, and the role of body composition in the global performance of transgender women athletes.

Objective: We aimed to compare the methodological quality of physical therapy–related trials published in open access with that of trials published in subscription-based journals, adjusting for subdiscipline, intervention type, endorsement of the Consolidated Standards of Reporting Trials, impact factor, and publication language. Design: In this meta-epidemiological study, we searched the Physiotherapy Evidence Database on May 8, 2021, to include any physical therapy–related trials published from January 1, 2020. We extracted variables such as Consolidated Standards of Reporting Trials endorsement, the Physiotherapy Evidence Database score, and publication type. We compared the Physiotherapy Evidence Database score between the publication types using a multivariable generalized estimating equation by adjusting for covariates. Results: A total of 2743 trials were included, with a mean total Physiotherapy Evidence Database score (standard deviation) of 5.8 (±1.5). Trials from open access journals had a lower total Physiotherapy Evidence Database score than those from subscription-based journals (5.5 ± 1.5 vs. 5.9 ± 1.5, mean difference = −0.4; 95% confidence interval = 0.3–0.5). Generalized estimating equation revealed that open access publication was significantly associated with the total Physiotherapy Evidence Database score (mean difference = −0.42; P < 0.001). Conclusions: In the recent physical therapy–related trials, open access publications demonstrated lower methodological quality than subscription-based publications, although with a small difference. [ABSTRACT FROM AUTHOR]

The considerable progress made in recent years in the diagnosis, risk stratification, and treatment of pulmonary hypertension was highlighted during the most recent edition of the Pulmonary Hypertension Association Scientific Sessions, which was held in Atlanta, Georgia from June 9 to 11, 2022, with the theme: Vision for the PHuture: The Evolving Science and Management of PH. Content presented over the 3‐day conference focused on scientific and management updates since the last sessions were held in 2018 and included didactic talks, debates, and roundtable discussions across a broad spectrum of topics related to pulmonary hypertension. This article aims to summarize the key messages from each of the session talks. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the influence of the biomodification of erosive lesions with a chitosan nanoformulation containing green tea (NanoCsQ) on the clinical performance of a composite resin. Methods: The study was performed in a split-mouth, randomized and double-blinded model with 20 patients with 40 erosive lesions. The patient's teeth were randomized into two groups (n=20) according to the surface treatment: 1) Without biomodification (control), and 2) Biomodification with NanoCsQ solution (experimental). The lesions were restored with adhesive (Tetric N-bond, Ivoclar) and composite resin (IPS Empress Direct, Ivoclar). The restorations were polished and 7 days (baseline), 6 months, and 12 months later were evaluated according to the United States Public Health Service (USPHS) modified criteria, using clinical exam and photographics. Data were analyzed by Friedman's and Wilcoxon signed-rank tests. Results: No significant differences were found between the control and experimental groups (p=0.423), and also among the follow-up periods (baseline, six months, and 12 months) (p=0.50). Regarding the retention criteria, 90% of the restoration had an alpha score in the control group. Only 10% of the restorations without biomodification (control) had a score charlie at the 12-month follow-up. None of the patients reported post-operatory sensitivity. Conclusion: The NanoCsQ solution did not negatively affect the performance of the composite resin restorations after 12 months. [ABSTRACT FROM AUTHOR]

Abstract The considerable progress made in recent years in the diagnosis, risk stratification, and treatment of pulmonary hypertension was highlighted during the most recent edition of the Pulmonary Hypertension Association Scientific Sessions, which was held in Atlanta, Georgia from June 9 to 11, 2022, with the theme: Vision for the PHuture: The Evolving Science and Management of PH. Content presented over the 3‐day conference focused on scientific and management updates since the last sessions were held in 2018 and included didactic talks, debates, and roundtable discussions across a broad spectrum of topics related to pulmonary hypertension. This article aims to summarize the key messages from each of the session talks.

Objective: The aim of the study was to identify the profile of clinical research related to orthopedic disorders worldwide. Methods: A survey of clinical research in orthopedics was performed in the ClinicalTrials.gov platform and Plataforma Brasil databases. Results: According to data from the ClinicalTrials.gov platform, 1.142 clinical trials related to orthopedic disorders were registered from January 2017 to July 2022. Brazil is in the 14th position in the international ranking, and the Universidade de Sao Paulo (USP) occupies the 6th position among the collaborators who performed the most research in this area. The importance of the foot and ankle area in clinical research related to orthopedic disorders is evident when it is the 7th most studied worldwide and the 2nd most studied in Brazil. Most clinical trials related to orthopedic disorders worldwide target the adult or older adult population and involve interventional studies. On the other hand, most of the clinical trials related to orthopedic disorders in Brazil target the pediatric or geriatric population and involve observational studies. Conclusion: The profile of clinical research related to orthopedic disorders worldwide showed that most clinical trials targeted the adult or older adult population and aimed to treat patients, not prevent diseases. Brazil targeted the pediatric or geriatric population focusing on characterizing populations and diseases. Clinical research related to orthopedic disorders performed worldwide and in Brazil depended on sponsorship and private institutions. Level of Evidence IV; Descriptive Observational Study.

Capturing these social drivers of health would help elucidate and contextualize health inequities; however, few CVD studies collect and report social and structural determinants of health. CVD mortality remains 30% higher for Black men and women[1] and Native Americans are 50% more likely to be diagnosed with CVD compared with their White counterparts. Keywords: cardiovascular diseases; clinical trials as topic; health equity; research EN cardiovascular diseases clinical trials as topic health equity research 204 206 3 07/20/23 20230718 NES 230718 Despite substantial investments in cardiovascular disease (CVD) research and groundbreaking advances in treatment, longstanding inequities in CVD outcomes persist among marginalized racial and ethnic groups. [Extracted from the article]

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily affects motor neurons in the brain and spinal cord. In the recent past, there have been just two drugs approved for treatment, riluzole and edaravone, which only prolong survival by a few months. However, there are many novel experimental drugs in development. In this review, we summarize 53 new drugs that have been evaluated in clinical trials from 2020 to 2022, which we have classified into eight mechanistic groups (anti-apoptotic, anti inflammatory, anti-excitotoxicity, regulated integrated stress response, neurotrophic factors and neuroprotection, anti-aggregation, gene therapy and other). Six were tested in phase 1 studies, 31 were in phase 2 studies, three failed in phase 3 studies and stopped further development, and the remaining 13 drugs were being tested in phase 3 studies, including methylcobalamin, masitinib, MN-166, verdiperstat, memantine, AMX0035, trazodone, CNM-Au8, pridopidine, SLS-005, IONN363, tofersen, and reldesemtiv. Among them, five drugs, including methylcobalamin, masitinib, AMX0035, CNM-Au8, and tofersen, have shown potent therapeutic effects in clinical trials. Recently, AMX0035 has been the third medicine approved by the FDA for the treatment of ALS after riluzole and edaravone. [ABSTRACT FROM AUTHOR]

Clinical trials across the pancreatic cancer journey Between 1 January 2012 and 31 December 2020, 136 pancreatic cancer clinical trials (not including trials focused exclusively on pancreatic neuroendocrine tumours) were conducted in at least one Australian investigational site. Limited access to clinical trials in pancreatic cancer Of the trials focused on pancreatic cancer, a large proportion of investigator-initiated trials were single-centre (10/25, 40%), and only four (16%) recruited internationally. Keywords: Cancer; Pancreatic diseases; Clinical trials as topic EN Cancer Pancreatic diseases Clinical trials as topic 505 509 5 11/14/22 20221115 NES 221115 Future clinical trials need to focus on the steps of the pancreatic cancer continuum which have been suboptimally explored Despite accounting for 2.8% of all new cancer cases diagnosed in Australia in 2021, pancreatic cancer contributed to 6.9% of all cancer-related deaths.1 This is due to its poor prognosis, with 50% of patients presenting with metastatic disease at diagnosis.2 In the period 2013-2017, the 5-year survival rate for pancreatic cancer was 11.5%, being among the lowest for all cancers and having only marginally improved from 10.7% in 2012-2016.1 Patients also experience high symptom burden across all stages of their cancer journey,3 which contributes to anxiety, depression and poor quality of life.4 The impact of pancreatic cancer combined with the urgent need to improve outcomes prompted the Australian Government to develop the I National Pancreatic Cancer Roadmap i .5 An important activity in informing the key priority areas of the roadmap was to undertake a review of clinical trials in pancreatic cancer to understand the gaps and opportunities in the current clinical trials landscape along the pancreatic cancer care continuum. [Extracted from the article]

The FDA's directive to deal with delayed confirmatory trials: lessons from pralatrexate and belinostat for T-cell lymphoma.

Patient recruitment is challenging for clinical trials. We introduce TrialGPT, an end-to-end framework for zero-shot patient-to-trial matching with large language models. TrialGPT comprises three modules: it first performs large-scale filtering to retrieve candidate trials (TrialGPT-Retrieval); then predicts criterion-level patient eligibility (TrialGPT-Matching); and finally generates trial-level scores (TrialGPT-Ranking). We evaluate TrialGPT on three cohorts of 183 synthetic patients with over 75,000 trial annotations. TrialGPT-Retrieval can recall over 90% of relevant trials using less than 6% of the initial collection. Manual evaluations on 1015 patient-criterion pairs show that TrialGPT-Matching achieves an accuracy of 87.3% with faithful explanations, close to the expert performance. The TrialGPT-Ranking scores are highly correlated with human judgments and outperform the best-competing models by 43.8% in ranking and excluding trials. Furthermore, our user study reveals that TrialGPT can reduce the screening time by 42.6% in patient recruitment. Overall, these results have demonstrated promising opportunities for patient-to-trial matching with TrialGPT., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The reduction in lung cancer mortality rates over the past decade can be partially ascribed to advancements in immunotherapy. Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape for advanced non-small cell lung cancer (NSCLC) and have recently been evaluated in multiple clinical trials to confirm their safety and efficacy in the neoadjuvant, adjuvant and perioperative settings for patients with resectable NSCLC. The Food and Drug Administration (FDA) has granted approval for adjuvant atezolizumab following platinum-doublet chemotherapy, neoadjuvant nivolumab and platinum-doublet chemotherapy, adjuvant pembrolizumab after platinum-doublet chemotherapy, and neoadjuvant/adjuvant pembrolizumab for resectable NSCLC, with potential forthcoming approvals for additional agents or indications. Novel data, approvals, and emerging research findings are dramatically shifting the accepted standards of care over just a few years. Despite these advances, the optimal application of these treatments is not entirely straightforward. This article summarizes the biological rationale for immunotherapy and the important clinical trials regarding perioperative ICIs. We also further outline the controversies and future directions to better guide the individualized treatment of NSCLC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Atherosclerosis (AS) is a chronic inflammatory disease characterized by the formation of atherosclerotic plaques that consist of numerous cells including smooth muscle cells, endothelial cells, immune cells, and foam cells. The most abundant innate and adaptive immune cells, including neutrophils, monocytes, macrophages, B cells, and T cells, play a pivotal role in the inflammatory response, lipoprotein metabolism, and foam cell formation to accelerate atherosclerotic plaque formation. In this review, we have discussed the underlying mechanisms of activated immune cells in promoting AS and reviewed published clinical trials for the treatment of AS by suppressing immune cell activation. We have also presented some crucial shortcomings of current clinical trials. Lastly, we have discussed the therapeutic potential of novel compounds, including herbal medicine and dietary food, in alleviating AS in animals. Despite these limitations, further clinical trials and experimental studies will enhance our understanding of the mechanisms modulated by immune cells and promote widespread drug use to treat AS by suppressing immune system-induced inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Clinical trials conducted by the Intergroup Rhabdomyosarcoma (RMS) Study Group and the Children's Oncology Group have been pivotal to establishing current standards for diagnosis and therapy for RMS. Recent advancements in understanding the biology and clinical behavior of RMS have led to more nuanced approaches to diagnosis, risk stratification, and treatment. The complexities introduced by these advancements, coupled with the rarity of RMS, pose challenges to conducting large-scale phase 3 clinical trials to evaluate new treatment strategies for RMS. Given these challenges, systematic planning of future clinical trials in RMS is paramount to address pertinent questions regarding the therapeutic efficacy of drugs, biomarkers of response, treatment-related toxicity, and patient quality of life. Herein, the authors outline the proposed strategic approach of the Children's Oncology Group Soft Tissue Sarcoma Committee to the next generation of RMS clinical trials, focusing on five themes: improved novel agent identification and preclinical to clinical translation, more efficient trial development and implementation, expanded opportunities for knowledge generation during trials, therapeutic toxicity reduction and quality of life, and patient engagement., (© 2024 American Cancer Society.)

Background: Early in the COVID-19 pandemic, numerous clinical trials were initiated. Although concerns were raised regarding the quality of the trials, the eventual research output yielded from the trials remains unknown. The objective of this study was to include all clinical trials registered on ClinicalTrials.gov during the first 6 months of the pandemic and assess if and where their results had been reported, their completion and discontinuation rates, achieved enrolment and changes made to the primary outcome after trial registration., Methods: We included all interventional studies related to COVID-19 first registered on ClinicalTrials.gov between 1 January 2020 and 1 July 2020. We systematically searched for trial results, reported through 15 May 2023, in scientific publications, preprints and ClinicalTrials.gov. We assessed the achieved trial enrolment, trial discontinuation (reaching <90% of target enrolment), and whether the primary outcome had been changed as compared with the initial protocol registration., Results: The 775 clinical trials included in the analysis planned to enrol 238 933 (median (IQR) 120 (60, 304) patients; 355 (46%) of the trials had reported results, and 283 (36%) were published in a scientific journal. In the reported trials, the total enrolment was 95 332 (median (IQR) 105 (45, 222) patients. 186 (24%) trials were completed, and 169 (22%) trials were discontinued, with slow recruitment being the most stated reason for discontinuation (9% of all trials, although 30% of the discontinued trials did not report a reason). 117 (33%) of the reported trials had changed their primary outcome. In total, 157 (20%) trials were completed and published in a scientific journal, of which 105 enrolled ≥100 patients and 103 had not changed the primary outcome. 63 completed and published trials enrolled ≥100 patients and had not changed the primary outcome., Conclusions: Most clinical trials of COVID-19 registered at ClinicalTrials.gov during the first 6 months of the pandemic remained unreported or had been discontinued. Many of the trials whose results had been reported enrolled few patients and changed the primary outcome after trial registration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Among the most powerful barriers to broader inclusion of diverse participants in clinical trials are social determinants of health, trustworthiness of health care providers and research institutions, and competing pressures on potential participants. Nevertheless, current tools to assess organizational capabilities for clinical trial diversity focus primarily on trial infrastructure, rely solely on quantitative self-reported data, and lack meaningful assessment of capabilities related to community engagement., Methods: The Equitable Breakthroughs in Medicine (EQBMED) initiative developed a holistic, collaborative, site-driven formative model and accompanying assessment to catalog sites' current capabilities and identify opportunities for growth in both conducting industry-sponsored clinical trials and enriching diversity of those trials. The model builds upon prior work and reflects unification of two historically distinct components-research operations and community engagement-since sustainable clinical trial diversity efforts must overcome these silos. Here we present the methodology we used to develop the model and accompanying assessment, describe how findings can support clinical trial diversity efforts, and report findings from early field testing at three U.S. sites., Results: The first three sites were diverse in size (e.g., < 250-1 K beds), with varying levels of clinical trial capabilities and community engagement. The maturity assessment laid the foundation for sites to identify and prioritize key areas to advance clinical trial diversity capabilities, and each has made tangible progress. In parallel to completing the assessment with these early sites to understand their maturity and set actionable goals, we also collected their feedback on content validity (e.g., clarity, comprehensiveness, terminology) and feasibility (e.g., ability to collect needed information and data, time required). We describe refinements made to improve the assessment and streamline the process. The EQBMED program will deploy the assessment across various site types (e.g., FQHCs, safety net hospitals) and make further refinements as warranted., Conclusions: Strategic investment in clinical trial diversity requires structured assessment of site maturity as a starting point for collaborative action. We propose the EQBMED maturity model as a first step toward informing efforts to increase representation of diverse populations in clinical research., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

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., Competing Interests: Competing interests Joseph Gleeson serves as a consultant for Ionis Pharmaceuticals, Neurocrine Pharmaceuticals, and the n-Lorem Foundation. Winston Yan is a founder, employee, and shareholder of Arbor Biotechnologies, and serves as President and Board Member of the N=1 Collaborative. Timothy Yu has received research support from EveryONE Medicines, and volunteer Board Member for the N=1 Collaborative, the Oligonucleotide Therapeutics Society, and the Society for RNA Therapeutics, and a volunteer advisor to several rare disease foundations. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Accurate, comprehensive, and consistent reporting of adverse events is of great importance for treatment decisions in clinical practice and patient safety. Aiming to evaluate the completeness and transparency of reported adverse events we conducted a retrospective analysis of completed clinical trials on glaucoma interventions registered in ClinicalTrials.gov from September 27, 2009, and updated and with results on or before November 1, 2023, as well as in corresponding journal publications. Any difference in completeness, number, or terminology/description of adverse events and all-cause mortality between ClinicalTrials.gov and the publication was categorized as inconsistent reporting of adverse events. All 79 trials with results both in the registry and a journal publication exhibited at least one inconsistency in reporting adverse events. In 19 publications (24%), the number of serious adverse events was smaller than in the registry. 69 (87%) trials reported more other adverse events in the registry than in the publication. Trials completed after the FDAA mandate for summary reporting of all-cause mortality more often reported this item in the registry but not in the publication. Trials on glaucoma interventions do not consistently report adverse events and thus introduce concerns about study credibility and potential harms of the interventions. Journals and other stakeholders in trial reporting must address this problem to ensure the safety of patients and trust in health interventions., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

We compare the clinical trial success rates of products receiving US Food and Drug Administration (FDA) accelerated approval (AA) to those approved without using this pathway. Our findings raise important questions about how the AA pathway can best optimize early access to therapeutics that are ultimately proven safe and effective., Competing Interests: Declaration of interests G.C.A. is past chair of the FDA’s Peripheral and Central Nervous System Advisory Committee and a co-founding principal and equity holder in Stage Analytics. These arrangements have been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

FDA Oncology Center's @Falleh&#95;Fallah and colleagues discuss loss of equipoise and other trial conduct challenges in an era of breakthrough therapies - via @JCO&#95;ASCO.

Unlocking the full potential of clinical trials through comprehensive CSR and IPD sharing can revolutionize cancer care, enhance safety evaluations, and reduce bias in systematic reviews. It is time for all stakeholders to embrace transparency and advance patient-centered outcomes.

Background: Increasing global interest in natural therapies has led to a rise in the use of herbal medicines for managing various ailments. However, concerns about scientific evaluation have prompted a study aiming to assess the study design of herbal medicine clinical trials. This study aimed to provide a descriptive overview of the study design, characteristics, and methodologies of contemporary herbal medicine clinical trials., Materials and Methods: The study reviewed herbal medicine clinical trials published between 2019 and 2022 in five electronic databases: PubMed, Embase, Web of Sciences, Scopus, and the Cochrane Library. Data extraction included study characteristics, intervention details, study design, outcome measures, trial phases, blinding, and other relevant information, with descriptive analyses presented. The term 'herbal medicines' in this study refers to herbs, herbal materials, preparations, and finished products containing active ingredients from plant parts or their combinations., Results: Out of the initially identified 5,918 records, 1,517 articles were eligible for inclusion in the study. The majority of herbal medicine clinical trials were conducted in Asian countries, covering a range of diseases. A randomized, double-blind, parallel design with a 1:1 allocation ratio was frequently employed, along with the common use of placebos across all trial phases. Capsules were the most common dosage form. The median number of human participants varied across trial phases, ranging from 50 in Phase 1 to 240 in Phase 4., Conclusions: The analysis observed that herbal medicine clinical trials employed randomized, double-blind, parallel designs, and the widespread use of placebo. Our observations provided valuable insights into the evolving landscape of herbal medicine clinical trials., (© 2024. The Author(s).)

Background: Melatonin's antioxidative and immune effects suggest potential in cancer therapy. This review assesses related clinical trials on ClinicalTrials.gov., Methods: All ClinicalTrials.gov trials registered up to January 17, 2024 were examined, focusing on trials that involved use of melatonin in cancer treatment. A 46 trials were summarized by their study status, study phase, study type, funder type and study results in the use of melatonin in cancer treatment., Results: The examination of the research data revealed a collective count of 46 clinical trials enlisted on ClinicalTrials.gov, all focus around the utilization of melatonin in cancer treatment. Among these, 24 trials had reached completion, constituting 91.3% of the entire trials, while 5 trials were presently in the recruitment phase, making up 10.8% of the total. None of these trials had received approval for marketing yet. The majority focus of the analysis encompassed interventional studies, around 42 trials and representing 91.3% of the overall trials, thereby incorporating most enrolled patients. In contrast, observational studies are a smaller fraction, comprising 4 trials (8.6% of the total), with a correspondingly lower number of involved patients. Regarding funding sources, most registered studies secured funding from diverse entities such as individuals, universities, and organizations, constituting 95.6% of all trials. In comparison, a minority of studies received funding from the National Institutes of Health, comprising 5 trials and accounting for 10.8% of the total trials., Conclusion: The analysis of 46 clinical trials on melatonin's use in cancer treatment reveals a significant importance on interventional studies. Overall, these findings contribute to the evolving understanding of melatonin's role in cancer treatment., Competing Interests: The authors declare no funding and conflicts of interest related to the content of this article., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)