Search

Black women with breast cancer often present with more aggressive disease compared with other races, contributing to an increased risk of cancer mortality. Despite this inequity, Black women remain severely underrepresented in breast cancer clinical trials. We aim to characterize factors that influence a woman's decision to enroll in a clinical trial, with the goal of identifying clinical interventions to aid in the recruitment of vulnerable groups. A cross-sectional, descriptive study was conducted using a questionnaire adapted from 2 prevalidated surveys investigating factors influencing clinical trial enrollment. The survey was administered to women with curable breast cancer during a single follow-up visit at 4 different sites within a university medical system where all patients are screened for clinical trial eligibility. Chi-square tests and Mann-Whitney U tests were used to assess associations or differences between the populations. One hundred ninety-four out of 209 women completed the survey, giving a compliance rate of 93%. Twenty-six percent of women self-identified as Black, most women were located at community sites (67.1%), most women had diagnoses of early-stage disease (I: 57.7%, II: 29.4%), and 81% of women had some collegiate-level education. Black women were younger at diagnosis (P =.005) and less likely to be married (P =.012) but more often lived with family members (P =.003) and had a lower median income (P <.001). According to the survey, Black women were less likely to trust their care team (P =.032), more likely to believe that research ultimately harms minorities (P <.001), and had a stronger belief in God's will determining illness and wellness (P <.001). Recurring themes of trust in the health care team, patient education, and advancement of cancer treatments were discussed in the focus groups. Failure to offer clinical trials and mistrust in research institutions may pose the greatest hindrances to the enrollment of Black women in clinical trials. Empowering women through education and fostering trustworthy relationships can encourage greater clinical trial participation. [ABSTRACT FROM AUTHOR]

Importance: Optimal health care delivery, both now and in the future, requires a continuous loop of knowledge generation, dissemination, and uptake on how best to provide care, not just determining what interventions work but also how best to ensure they are provided to those who need them. The randomized clinical trial (RCT) is the most rigorous instrument to determine what works in health care. However, major issues with both the clinical trials enterprise and the lack of integration of clinical trials with health care delivery compromise medicine's ability to best serve society. Observations: In most resource-rich countries, the clinical trials and health care delivery enterprises function as separate entities, with siloed goals, infrastructure, and incentives. Consequently, RCTs are often poorly relevant and responsive to the needs of patients and those responsible for care delivery. At the same time, health care delivery systems are often disengaged from clinical trials and fail to rapidly incorporate knowledge generated from RCTs into practice. Though longstanding, these issues are more pressing given the lessons learned from the COVID-19 pandemic, heightened awareness of the disproportionate impact of poor access to optimal care on vulnerable populations, and the unprecedented opportunity for improvement offered by the digital revolution in health care. Four major areas must be improved. First, especially in the US, greater clarity is required to ensure appropriate regulation and oversight of implementation science, quality improvement, embedded clinical trials, and learning health systems. Second, greater adoption is required of study designs that improve statistical and logistical efficiency and lower the burden on participants and clinicians, allowing trials to be smarter, safer, and faster. Third, RCTs could be considerably more responsive and efficient if they were better integrated with electronic health records. However, this advance first requires greater adoption of standards and processes designed to ensure health data are adequately reliable and accurate and capable of being transferred responsibly and efficiently across platforms and organizations. Fourth, tackling the problems described above requires alignment of stakeholders in the clinical trials and health care delivery enterprises through financial and nonfinancial incentives, which could be enabled by new legislation. Solutions exist for each of these problems, and there are examples of success for each, but there is a failure to implement at adequate scale. Conclusions and Relevance: The gulf between current care and that which could be delivered has arguably never been wider. A key contributor is that the 2 limbs of knowledge generation and implementation—the clinical trials and health care delivery enterprises—operate as a house divided. Better integration of these 2 worlds is key to accelerated improvement in health care delivery. This Special Communication discusses the need for better integration of clinical trials and health care delivery enterprises. [ABSTRACT FROM AUTHOR]

Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications. [ABSTRACT FROM AUTHOR]

This article explores the benefits and challenges of conducting pragmatic trials using electronic health records (EHRs). Pragmatic trials are crucial for informing clinical practice when there is limited data available. EHRs offer advantages such as accessibility and the ability to enroll large numbers of patients quickly. However, there are unique challenges in conducting EHR-enabled trials, including potential biases and contamination of treatment groups. Real-time monitoring of enrollment and safety events is also difficult. Despite these challenges, EHR-enabled trials have shown promising results in various fields. The article emphasizes the importance of careful planning, monitoring, and validation of data in EHR-enabled trials to ensure accurate and reliable results. It also discusses the potential benefits and limitations of EHR-enabled trials in improving patient care. [Extracted from the article]

Background: On-site monitoring is a crucial component of quality control in clinical trials. However, many cast doubt on its cost-effectiveness due to various issues, such as a lack of monitoring focus that could assist in prioritizing limited resources during a site visit. Consequently, an increasing number of trial sponsors are implementing a hybrid monitoring strategy that combines on-site monitoring with centralised monitoring. One of the primary objectives of centralised monitoring, as stated in the clinical trial guidelines, is to guide and adjust the extent and frequency of on-site monitoring. Quality tolerance limits (QTLs) introduced in ICH E6(R2) and thresholds proposed by TransCelerate Biopharma are two existing approaches for achieving this objective at the trial- and site-levels, respectively. The funnel plot, as another threshold-based site-level method, overcomes the limitation of TransCelerate's method by adjusting thresholds flexibly based on site sizes. Nonetheless, both methods do not transparently explain the reason for choosing the thresholds that they used or whether their choices are optimal in any certain sense. Additionally, related Bayesian monitoring methods are also lacking. Methods: We propose a simple, transparent, and user-friendly Bayesian-based risk boundary for determining the extent and frequency of on-site monitoring both at the trial- and site-levels. We developed a four-step approach, including: 1) establishing risk levels for key risk indicators (KRIs) along with their corresponding monitoring actions and estimates; 2) calculating the optimal risk boundaries; 3) comparing the outcomes of KRIs against the optimal risk boundaries; and 4) providing recommendations based on the comparison results. Our method can be used to identify the optimal risk boundaries within an established risk level range and is applicable to continuous, discrete, and time-to-event endpoints. Results: We evaluate the performance of the proposed risk boundaries via simulations that mimic various realistic clinical trial scenarios. The performance of the proposed risk boundaries is compared against the funnel plot using real clinical trial data. The results demonstrate the applicability and flexibility of the proposed method for clinical trial monitoring. Moreover, we identify key factors that affect the optimality and performance of the proposed risk boundaries, respectively. Conclusion: Given the aforementioned advantages of the proposed risk boundaries, we expect that they will benefit the clinical trial community at large, in particular in the realm of risk-based monitoring. [ABSTRACT FROM AUTHOR]

Background: In recent years, alternative monitoring approaches, such as risk-based and remote monitoring techniques, have been recommended instead of traditional on-site monitoring to achieve more efficient monitoring. Remote risk-based monitoring (R2BM) is a monitoring technique that combines risk-based and remote monitoring and focuses on the detection of critical data and process errors. Direct data capture (DDC), which directly collects electronic source data, can facilitate R2BM by minimizing the extent of source documents that must be reviewed and reducing the additional workload on R2BM. In this study, we evaluated the effectiveness of R2BM and the synergistic effect of combining R2BM with DDC. Methods: R2BM was prospectively conducted with eight participants in a randomized clinical trial using a remote monitoring system that uploaded photographs of source documents to a cloud location. Critical data and processes were verified by R2BM, and later, all were confirmed by on-site monitoring to evaluate the ability of R2BM to detect critical data and process errors and the workload of uploading photographs for clinical trial staff. In addition, the reduction of the number of uploaded photographs was evaluated by assuming that the DDC was introduced for data collection. Results: Of the 4645 data points, 20.9% (n = 973, 95% confidence interval = 19.8–22.2) were identified as critical. All critical data errors corresponding to 5.4% (n = 53/973, 95% confidence interval = 4.1–7.1) of the critical data and critical process errors were detectable by R2BM. The mean number of uploaded photographs and the mean time to upload them per visit per participant were 34.4 ± 11.9 and 26.5 ± 11.8 min (mean ± standard deviation), respectively. When assuming that DDC was introduced for data collection, 45.0% (95% confidence interval = 42.2–47.9) of uploaded photographs for R2BM were reduced. Conclusions: R2BM can detect 100% of the critical data and process errors without on-site monitoring. Combining R2BM with DDC reduces the workload of R2BM and further improves its efficiency. [ABSTRACT FROM AUTHOR]

Purpose: There is a lack of evidence regarding how patients with malignant brain tumor and their relatives experience participation in neurooncological clinical trials. Similarly, insights from the perspective of trial staff caring for this group of patients are missing. This study aims to investigate patient, relative and trial staff experiences regarding participation in clinical neurooncological trials. Methods: Within a qualitative exploratory study, 29 semi-structured interviews with brain tumor patients, relatives and trial staff were conducted and analyzed using reflexive thematic analysis (RTA) by Braun and Clarke. A patient researcher and patient council were involved in data analysis and interpretation. Results: Four themes were developed reflecting significant aspects of the trial experience: 1. "It all revolves around hope"; 2. "Trial participation: experiencing unique medical care"; 3. "Everyone's roles are changing"; 4. "Communication as a possible area of conflict". Experiencing trial participation and general medical treatment were found to be interconnected to such a degree that they were often not meaningfully distinguished by patients and relatives. Conclusion: In addition to assessing traditional endpoints for patient outcomes, we recommend increased emphasis on investigating the impact of the "soft" components constituting trial participation. Due to the interconnectedness of medical treatment and trial participation, we recommend further investigation in comparison to experiences in regular care. A deeper understanding of trial participation is needed to inform improvements for patient experiences and staff satisfaction alongside medical and scientific progress. Plain Language Summary: The treatment options available to patients with (malignant) brain tumors are currently very limited. Therefore, patients are sometimes offered to participate in a clinical trial. This means that they receive an experimental treatment (eg new medicine) for which it is not yet clear whether it works better than regular medical care. Currently, little is known about how this group of patients, their relatives and the hospital staff who care for them experience the participation in these clinical trials – which is what we aimed to explore in our study reported here. Based on interviews with patients, relatives and staff, we found that:trial participation mainly revolves around hope;trial participation entails experiencing unique medical care;trial participation significantly changes the previous roles of patients, relatives and staff;trial participation intensifies communication as a possible area of conflict. By providing information on how patients, relatives and staff make sense of their trial experiences, this study constitutes an important addition to the traditional focus of clinical trials on medical and scientific endpoints (eg progression-free survival). This may help clinicians and researchers involved in cancer research and treatment to understand why "unsuccessful" trials can still be perceived as positive by patients or how hopeful communication may support their patients even when perceived as "unrealistic" from the clinicians' perspective. An in depth understanding of trial participation from the perspective of those affected is needed for improved care experiences alongside medical and scientific progress for cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Poor representation of pregnant and lactating women and people in clinical trials has marginalised their health concerns and denied the maternal–fetal/infant dyad benefits of innovation in therapeutic research and development. This mixed-methods systematic review synthesised factors affecting the participation of pregnant and lactating women in clinical trials, across all levels of the research ecosystem. Methods and findings: We searched 8 databases from inception to 14 February 2024 to identify qualitative, quantitative, and mixed-methods studies that described factors affecting participation of pregnant and lactating women in vaccine and therapeutic clinical trials in any setting. We used thematic synthesis to analyse the qualitative literature and assessed confidence in each qualitative review finding using the GRADE-CERQual approach. We compared quantitative data against the thematic synthesis findings to assess areas of convergence or divergence. We mapped review findings to the Theoretical Domains Framework (TDF) and Capability, Opportunity, and Motivation Model of Behaviour (COM-B) to inform future development of behaviour change strategies. We included 60 papers from 27 countries. We grouped 24 review findings under 5 overarching themes: (a) interplay between perceived risks and benefits of participation in women's decision-making; (b) engagement between women and the medical and research ecosystems; (c) gender norms and decision-making autonomy; (d) factors affecting clinical trial recruitment; and (e) upstream factors in the research ecosystem. Women's willingness to participate in trials was affected by: perceived risk of the health condition weighed against an intervention's risks and benefits, therapeutic optimism, intervention acceptability, expectations of receiving higher quality care in a trial, altruistic motivations, intimate relationship dynamics, and power and trust in medicine and research. Health workers supported women's participation in trials when they perceived clinical equipoise, had hope for novel therapeutic applications, and were convinced an intervention was safe. For research staff, developing reciprocal relationships with health workers, having access to resources for trial implementation, ensuring the trial was visible to potential participants and health workers, implementing a woman-centred approach when communicating with potential participants, and emotional orientations towards the trial were factors perceived to affect recruitment. For study investigators and ethics committees, the complexities and subjectivities in risk assessments and trial design, and limited funding of such trials contributed to their reluctance in leading and approving such trials. All included studies focused on factors affecting participation of cisgender pregnant women in clinical trials; future research should consider other pregnancy-capable populations, including transgender and nonbinary people. Conclusions: This systematic review highlights diverse factors across multiple levels and stakeholders affecting the participation of pregnant and lactating women in clinical trials. By linking identified factors to frameworks of behaviour change, we have developed theoretically informed strategies that can help optimise pregnant and lactating women's engagement, participation, and trust in such trials. Using a mixed-methods approach, Mridula Shankar and colleagues investigate the reasons why those who are pregnant and breastfeeding are under-represented in clinical trials. Author summary: Why was this study done?: Pregnant and lactating women and people are routinely excluded from participating in drug and vaccine clinical trials, resulting in limited options for prevention and treatment of medical conditions. Challenges to including pregnant and lactating women and people in clinical research have been identified at multiple levels of the research and health systems, but the full range of barriers and facilitators to participation are not well known. What did the researchers do and find?: We conducted a mixed-methods systematic review and identified 60 research articles from 27 countries on the views and experiences of pregnant and lactating women's participation in clinical research, from the perspectives of cisgender women, family and community members, health workers, and people involved in the conduct of clinical research. Using a thematic synthesis approach, we identified barriers affecting participation including women having a limited appetite for risk during pregnancy and lactation, concerns about women's bodily autonomy during pregnancy, and challenges in obtaining ethical approval for clinical research with pregnant women. We also identified facilitators of participation including the potential for personal health benefits, expectations of higher quality care, trust in the medical and research systems, and strong teamwork between researchers and health workers. What do these findings mean?: Our findings demonstrate the need for multipronged strategies to address barriers and reinforce facilitators across the various levels of the research and health systems. The actions that are needed to overcome these barriers and reinforce facilitators must be discussed, prioritised, and adapted to specific contexts. All included studies focused on factors affecting participation of cisgender pregnant women in clinical trials; future research should consider other pregnancy-capable populations, including transgender and nonbinary people. [ABSTRACT FROM AUTHOR]

Clinical trial participation continues to be low, slowing new cancer therapy development. Few strategies have been prospectively tested to address barriers to enrollment. We investigated the effectiveness of a physician audit and feedback report to improve clinical trial enrollment. We conducted a randomized quality improvement study among radiation oncologists at a multisite tertiary cancer network. Physicians in the intervention group received quarterly audit and feedback reports comparing the physician's trial enrollments with those of their peers. The primary outcome was trial enrollments. Among physicians randomized to receive the feedback report (n = 30), the median proportion of patients enrolled during the study period increased to 6.1% (IQR, 2.6%-9.3%) from 3.2% (IQR, 1.1%-10%) at baseline. Among those not receiving the feedback report (n = 29), the median proportion of patients enrolled increased to 4.1% (IQR, 1.3%-7.6%) from 1.6% (IQR, 0%-4.1%) at baseline. There was a nonsignificant change in the proportion of enrollments associated with receiving the feedback report (−0.6%; 95% CI, −3.0% to 1.8%; P =.6). Notably, there was an interaction between baseline trial accrual and receipt of feedback reports (P =.005), with enrollment declining among high accruers. There was an increase in enrollment throughout the study, regardless of study group (P =.001). In this study, a positive effect of physician audit and feedback on clinical trial enrollment was not observed. Future efforts should avoid disincentivizing high accruers and might consider pairing feedback with other patient- or physician-level strategies. The increase in trial enrollment in both groups over time highlights the importance of including a comparison group in quality improvement studies to reduce confounding from secular trends. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic led to widespread disruption and termination of clinical research and a prompt adoption of mobile health (mHealth) technologies in the healthcare space. As the United States' healthcare system has rapidly become reliant on remotely conducted activities, the implementation of decentralized methods using mHealth technology in research investigation has become a necessary alternative to traditional in-person cohort studies. The aim of this article is to: report successful and unsuccessful examples of remote asthma clinical studies, explore the benefits and potential drawbacks of virtual clinical investigation, discuss the potential impact on equity and representation in asthma research, and provide suggestions through which investigators can implement decentralized clinical trials. Enhanced study accessibility, participant diversity, safety measures, and research efficacy are some of the benefits identified with a focused discussion on the impact on equity that decentralized clinical trials renders. Furthermore, potential concerns regarding regulatory compliance, data privacy, and effective mHealth design and solutions are discussed. Despite the setbacks and interruptions faced by the study participants and investigators due to the pandemic, the transition to decentralized clinical studies using mHealth technology is a positive, feasible step toward innovation and equity in the allergy and immunology field. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy, the most common childhood muscular dystrophy, is caused by dystrophin deficiency. Preclinical and phase 2 study data have suggested that givinostat, a histone deacetylase inhibitor, might help to counteract the effects of this deficiency. We aimed to evaluate the safety and efficacy of givinostat in the treatment of Duchenne muscular dystrophy. This multicentre, randomised, double-blind, placebo-controlled, phase 3 trial was done at 41 tertiary care sites in 11 countries. Eligible participants were ambulant, male, and aged at least 6 years, had a genetically confirmed diagnosis of Duchenne muscular dystrophy, completed two four-stair climb assessments with a mean of 8 s or less (≤1 s variance), had a time-to-rise of at least 3 s but less than 10 s, and had received systemic corticosteroids for at least 6 months. Participating boys were randomly assigned (2:1, allocated according to a list generated by the interactive response technology provider) to receive either oral givinostat or matching placebo twice a day for 72 weeks, stratified by concomitant steroid use. Boys, investigators, and site and sponsor staff were masked to treatment assignment. The dose was flexible, based on weight, and was reduced if not tolerated. Boys were divided into two groups on the basis of their baseline vastus lateralis fat fraction (VLFF; measured by magnetic resonance spectroscopy): group A comprised boys with a VLFF of more than 5% but no more than 30%, whereas group B comprised boys with a VLFF of 5% or less, or more than 30%. The primary endpoint compared the effects of givinostat and placebo on the change in results of the four-stair climb assessment between baseline and 72 weeks, in the intention-to-treat, group A population. Safety was assessed in all randomly assigned boys who received at least one dose of study drug. When the first 50 boys in group A completed 12 months of treatment, an interim futility assessment was conducted, after which the sample size was adapted using masked data from the four-stair climb assessments. Furthermore, the starting dose of givinostat was reduced following a protocol amendment. This trial is registered with ClinicalTrials.gov , NCT02851797 , and is complete. Between June 6, 2017, and Feb 22, 2022, 359 boys were assessed for eligibility. Of these, 179 were enrolled into the study (median age 9·8 years [IQR 8·1–11·0]), all of whom were randomly assigned (118 to receive givinostat and 61 to receive placebo); 170 (95%) boys completed the study. Of the 179 boys enrolled, 120 (67%) were in group A (81 givinostat and 39 placebo); of these, 114 (95%) completed the study. For participants in group A, comparing the results of the four-stair climb assessment at 72 weeks and baseline, the geometric least squares mean ratio was 1·27 (95% CI 1·17–1·37) for boys receiving givinostat and 1·48 (1·32–1·66) for those receiving placebo (ratio 0·86, 95% CI 0·745–0·989; p=0·035). The most common adverse events in the givinostat group were diarrhoea (43 [36%] of 118 boys vs 11 [18%] of 61 receiving placebo) and vomiting (34 [29%] vs 8 [13%]); no treatment-related deaths occurred. Among ambulant boys with Duchenne muscular dystrophy, results of the four-stair climb assessment worsened in both groups over the study period; however, the decline was significantly smaller with givinostat than with placebo. The dose of givinostat was reduced after an interim safety analysis, but no new safety signals were reported. An ongoing extension study is evaluating the long-term safety and efficacy of givinostat in patients with Duchenne muscular dystrophy. Italfarmaco. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Recruitment of sufficient and diverse participants into clinical research for Alzheimer's disease and related dementias remains a formidable challenge. The primary goal of this manuscript is to provide an overview of an approach to diversifying research recruitment and to provide case examples of several methods for achieving greater diversity in clinical research enrollment. METHODS: The University of Kansas Alzheimer's Disease Research Center (KU ADRC) developed MyAlliance for Brain Health (MyAlliance), a service‐oriented recruitment model. MyAlliance comprises a Primary Care Provider Network, a Patient and Family Network, and a Community Organization Network, each delivering tailored value to relevant parties while facilitating research referrals. RESULTS: We review three methods for encouraging increased diversity in clinical research participation. Initial outcomes reveal an increase in underrepresented participants from 17% to 27% in a research registry. Enrollments into studies supported by the research registry experienced a 51% increase in proportion of participants from underrepresented communities. DISCUSSION: MyAlliance shifts power, resources, and knowledge to community advocates, promoting brain health awareness and research participation, and demands substantial financial investment and administrative commitment. MyAlliance offers valuable lessons for building sustainable, community‐centered research recruitment infrastructure, emphasizing the importance of localized engagement and cultural understanding. Highlights: MyAlliance led to a significant increase in the representation of underrepresented racial and ethnic groups and individuals from rural areas.The service‐oriented approach facilitated long‐term community engagement and trust‐building, extending partnerships between an academic medical center and community organizations.While effective, MyAlliance required substantial financial investment, with costs including infrastructure development, staff support, partner organization compensation, and promotional activities, underscoring the resource‐intensive nature of inclusive research recruitment efforts. [ABSTRACT FROM AUTHOR]

The article discusses the need for equitable access to clinical trials for individuals with respiratory conditions, particularly those who live outside major cities. It highlights the disproportionate burden of respiratory diseases on people in rural and remote areas, citing examples from Asia, the United States, and Australia. The article emphasizes the importance of clinical trials in providing early access to new therapies and technologies, but notes that participation rates are lower in regional areas due to the concentration of trial sites in major cities. It suggests that teletrials, which use telehealth to enable remote access to clinical trials, could be a solution to this issue. The article references the successful implementation of teletrials in other specialties, such as oncology, and discusses the potential benefits of teletrials in respiratory medicine, including increased diversity of participants, decreased recruitment time, enhanced retention, and reduced costs for patients. It also highlights the investment and infrastructure development for teletrials in Australia, which could serve as a model for other jurisdictions. The article concludes by urging respiratory clinical triallists to seize the opportunities presented by teletrials to expand access to clinical trials for individuals with respiratory diseases who live outside major cities. [Extracted from the article]

Background: Economic evaluations alongside implementation trials compare the outcomes and costs of competing implementation strategies to identify the most efficient strategies. The aims of this systematic review were to investigate how economic evaluations are performed in randomized implementation trials in clinical settings and to assess the quality of these evaluations. Methods: A systematic literature review was conducted on 23 March 2023 to identify studies that reported on economic evaluations embedded in randomized implementation trials in clinical settings. A systematic search was applied across seven databases, and references of relevant reviews were screened for additional studies. The Drummond Checklist was used to assess the quality and risk of bias of included economic evaluations. Study characteristics and quality assessments were tabulated and described. Results: Of the 6,550 studies screened for eligibility, 10 met the inclusion criteria. Included studies were published between 1990 and 2022 and from North America, the United Kingdom, Europe, and Africa. Most studies were conducted in the primary and out-patient care setting. Implementation costs included materials, staffing, and training, and the most common approach to collecting implementation costs was obtaining expense and budget reports. Included studies scored medium to high in terms of economic methodological quality. Conclusions: Economic evidence is particularly useful for healthcare funders and service providers to inform the prioritization of implementation efforts in the context of limited resources and competing demands. The relatively small number of studies identified may be due to lack of guidance on how to conduct economic evaluations alongside implementation trials and the lack of standardized terminology used to describe implementation strategies in clinical research. We discuss these methodological gaps and present recommendations for embedding economic evaluations in implementation trials. First, reporting implementation strategies used in clinical trials and aligning these strategies with implementation outcomes and costs are an important advancement in clinical research. Second, economic evaluations of implementation trials should follow guidelines for standard clinical trial economic evaluations and adopt an appropriate costing and data collection approach. Third, hybrid trial designs are recommended to generate evidence for effective and cost-effective implementation strategies alongside clinical effectiveness and cost-effectiveness. Trial registration: The review was prospectively registered with PROSPERO (CRD42023410186). [ABSTRACT FROM AUTHOR]

Effective implementation of cancer screening programs can reduce diseasespecific incidence and mortality. Screening is currently recommended for breast, cervical, colorectal and lung cancer. However, initial and repeat adherence to screening tests in accordance with current guidelines is suboptimal, with the lowest rates observed in historically underserved groups. If used in concert with recommended cancer screening tests, new biospecimen-based multi-cancer early detection (MCED) tests could help to identify more cancers that may be amendable to effective treatment. Clinical trials designed to assess the safety and efficacy of MCED tests to assess their potential for reducing cancer mortality are needed and many are underway. In the conduct of MCED test trials, it is crucial that participant recruitment efforts successfully engage participants from diverse populations experiencing cancer disparities. Strategic partnerships involving health systems, clinical practices, and communities can increase the reach of MCED trial recruitment efforts among populations experiencing disparities. This goal can be achieved by developing health system-based learning communities that build understanding of and trust in biomedical research; and by applying innovative methods for identifying eligible trial patients, educating potential participants about research trials, and engaging eligible individuals in shared decision making (SDM) about trial participation. This article describes how a developing consortium of health systems has used this approach to encourage the uptake of cancer screening in a wide range of populations and how such a strategy can facilitate the enrollment of persons from diverse patient and community populations in MCED trials. [ABSTRACT FROM AUTHOR]

The probability life distributions usually describe the time to event or survival time. Therefore, these life distributions play a crucial role in the analysis and projection of the maximum life expectancy using the Laplace transform technique for nonparametric hypothesis testing. A flexible framework for monitoring randomized clinical trials utilizing prior knowledge of certain phenomena under uncertainty is provided by the Laplace transform. By considering the previous data, medical professionals can also utilize these estimators to calculate the chance of tumor recurrence, cardiovascular death, and AIDS for HIV patients. However, censoring occurs in clinical trials and medical studies when the precise event's time of occurrence is unknown. The present study aims to propose a new test for exponential better than used (EBU). The suggested statistical test's efficiency and critical values are computed and compared with those of previous classes. Furthermore, the suggested test statistic is provided in bivariate form as well. Finally, the methodology is then tested using medical data in order to provide evidence that it is applied efficiently. [ABSTRACT FROM AUTHOR]

Background: Clinical trials of traditional Chinese medicine (TCM) and Western medicine showed there was heterogeneity of outcome reporting in myocardial infarction (MI). Developing a core outcome set (COS) might improve the consistency of outcome reporting in future clinical trials. Methods: A list of outcomes was developed based on a systematic review of randomized controlled trials (RCTs) of MI and semistructured interviews with MI patients. Two rounds of Delphi survey for clinicians, researchers, journal editors, and methodologists were conducted. An online questionnaire sent to nurses. After an online consensus meeting, a COS for MI RCTs was developed. Results: After extracted data from clinical trials and discussed, 216 outcomes were included in round 1 of the Delphi survey. Seventy‐four participants completed round 1 of the Delphi survey. Sixty‐five participants completed round 2 of the Delphi survey. Twenty‐two nurses completed the online questionnaire. Fifteen participants attended the online consensus meeting, and 14 of them voted and determined the final COS. For all types of MI, it was recommended that left ventricular ejection fraction and quality of life be measured and reported. For acute MI, the participants in the consensus meeting recommended the following core outcomes: death from cardio‐cerebrovascular disease, cardiogenic shock, heart failure, troponin I, troponin T, creatine kinase isoenzyme, Killip class, target vessel revascularization, and emergency CABG. For previous MI, recurrent MI, recurrent angina pectoris, and heart failure readmission were recommended. Conclusions: The COS for MI in RCTs provides recommendations for clinical trials that seek to improve outcomes for patients with MI. [ABSTRACT FROM AUTHOR]

Patients, families, healthcare providers and funders face multiple comparable treatment options without knowing which provides the best quality of care. As a step towards improving this, the REthinking Clinical Trials (REaCT) pragmatic trials program started in 2014 to break down many of the traditional barriers to performing clinical trials. However, until other innovative methodologies become widely used, the impact of this program will remain limited. These innovations include the incorporation of near equivalence analyses and the incorporation of artificial intelligence (AI) into clinical trial design. Near equivalence analyses allow for the comparison of different treatments (drug and non-drug) using quality of life, toxicity, cost-effectiveness, and pharmacokinetic/pharmacodynamic data. AI offers unique opportunities to maximize the information gleaned from clinical trials, reduces sample size estimates, and can potentially "rescue" poorly accruing trials. On 2 May 2023, the first REaCT international symposium took place to connect clinicians and scientists, set goals and identify future avenues for investigator-led clinical trials. Here, we summarize the topics presented at this meeting to promote sharing and support other similarly motivated groups to learn and share their experiences. [ABSTRACT FROM AUTHOR]

This document discusses the increase in pharmaceutical clinical trials conducted abroad and the need for regulation to protect participants and ensure the validity of data. It highlights the benefits and drawbacks of conducting trials in foreign countries, particularly in low- and middle-income countries. The document also addresses ethical concerns such as informed consent, language barriers, and cultural differences that can affect participants' understanding and decision-making. It emphasizes the importance of effective oversight and enforcement of regulations, as well as the need for remedies for participants who are harmed. The document concludes by emphasizing the importance of global health and the interconnectedness of countries in clinical research. [Extracted from the article]

The lack of treatments with durable response in neuro-oncology highlights the critical need for clinical trials to advance patient care. The intersection of relatively low incidence, evolving classification schema, and entrenched community, healthcare provider, and organizational factors have been historic challenges against successful trial enrollment and implementation. The additional need for multidisciplinary, often tertiary-level care, further magnifies latent national and international health inequities with rural and under-served populations. The COVID-19 pandemic both unveiled fundamental weaknesses in historical approaches and prompted the necessity of new approaches and systems for conducting clinical trials. Here, we provide an overview of traditional barriers to clinical trial enrollment in neuro-oncology, the effect of COVID-19 on these barriers, and the discovery of additional systemic weaknesses. Finally, we discuss future directions by reflecting on lessons learned with strategies to broaden access of care and streamline clinical trial integration into clinical practice. [ABSTRACT FROM AUTHOR]

Fewer than half of patients treated with hemodialysis survive 5 years. Multiple therapeutics are used to address the complications of advanced chronic kidney disease but most have not been found to improve clinical outcomes. Clinical trials of treatment innovations for chronic kidney diseases and dialysis care have been suboptimal in number and quality. Recent trials are changing this trend. Practice and policy change when new evidence emerges remains frequently impeded by resource and organizational constraints and accordingly, clinical practice guidelines are updated years or decades after definitive evidence is produced. Ultimately, practice change in health systems is slow, leading to impaired uptake of effective medical interventions and lower value healthcare, although innovations in rapid guideline production are emerging. What can be done to ensure that conclusive evidence is taken up in practice, policy and healthcare funding? We use the example of the recently published hard endpoint study "Comparison of high-dose HDF with high-flux HD" (CONVINCE) (hemodiafiltration versus hemodialysis), to explain how a new trial can impact on medical knowledge and change in practices. We (i) assess how the trial can be placed in the context of the totality of the evidence, (ii) define whether or not further trials of convective dialysis therapies are still needed and (iii) examine whether the evidence for convective therapies is now ready to inform practice, policy and funding change. When looking at CONVINCE in the context of the totality of evidence, we show that it addresses dialysis quality improvement priorities and is consistent with other trials evaluating convective dialysis therapies, and that the evidence for convective dialysis therapies is now definitive. Once updated evidence for cost-effectiveness in specific healthcare settings and patient-reported outcomes become available, we should therefore determine whether or not clinical practice guidelines should recommend uptake of convective dialysis therapies routinely, and move on to evaluating other treatments. [ABSTRACT FROM AUTHOR]

Background: A lack of onsite clinical trials is the largest barrier to participation of cancer patients in trials. Development of an automated process for regional trial eligibility screening first requires identification of patient electronic health record data that allows effective trial screening, and evidence that searching for trials regionally has a positive impact compared with site‐specific searching. Methods: To assess a screening framework that would support an automated regional search tool, a set of patient clinical variables was analyzed for prescreening clinical trials. The variables were used to assess regional compared with site‐specific screening throughout the United States. Results: Eight core variables from patient electronic health records were identified that yielded likely matches in a prescreen process. Assessment of the screening framework was performed using these variables to search for trials locally and regionally for an 84‐patient cohort. The likelihood that a trial returned in this prescreen was a provisional trial match was 45.7%. Expanding the search radius to 20 miles led to a net 91% increase in matches across cancers within the tested cohort. In a U.S. regional analysis, for sparsely populated areas, searching a 100‐mile radius using the prescreening framework was needed, whereas for urban areas a 20‐mile radius was sufficient. Conclusion: A clinical trial screening framework was assessed that uses limited patient data to efficiently and effectively identify prescreen matches for clinical trials. This framework improves trial matching rates when searching regionally compared with locally, although the applicability of this framework may vary geographically depending on oncology practice density. Plain Language Summary: Clinical trials provide cancer patients the opportunity to participate in research and development of new drugs and treatment approaches. It can be difficult to find available clinical trials for which a patient is eligible.This article describes an approach to clinical trial matching using limited patient data to search for trials regionally, beyond just the patient's local care site.Feasibility testing shows that this process can lead to a net 91% increase in the number of potential clinical trial matches available within 20 miles of a patient.Based on these findings, a software tool based on this model is being developed that will automatically send limited, deidentified information from patient medical records to services that can identify possible clinical trials within a given region. To increase patient access to clinical trials, a prescreening framework was developed using deidentified data elements extracted from patient electronic health records to identify likely clinical trials in a regional manner. Feasibility testing shows that this framework effectively performs trial eligibility screening using limited patient data and improves trial matching rates because of regional search capability. [ABSTRACT FROM AUTHOR]

Background: Provider and institutional practices have been shown to have a large impact on cancer clinical trial enrollment. Understanding provider perspectives on screening for trial eligibility is necessary to improve enrollment. Methods: A questionnaire about incentives, barriers, process tools, and infrastructure related to opening trials and referring patients to onsite and offsite trials was administered to diverse stakeholders, including professional societies, advocacy organizations, and industry networks. Descriptive statistics were used to summarize findings. Results: Overall, 693 responses were received, primarily from physicians (42.7%) and nurses (35.6%) employed at hospital health systems (43.7%) and academic centers (36.5%). Approximately half (49.2%) screened all patients for onsite clinical trials with screening typically done by manual chart review (81.9%). The greatest incentive reported for offering trials was providing the best treatment options for patients (67.7%). Contracting and paperwork (48.5%) were the greatest barriers to opening more onsite trials. Offsite referrals were rare. Conclusions: Screening for trial eligibility is a largely manual and ad hoc process, with screening and referral to offsite trials occurring infrequently. Administrative and infrastructure barriers commonly prevent sites from opening more onsite trials. These findings suggest that automated trial screening tools built into workflows that screen in a site‐agnostic manner could result in more frequent trial eligibility screening, especially for offsite trials. With recent momentum, in part in response to the COVID‐19 pandemic, to improve clinical trial efficiencies and broaden access and participant diversity, implementing tools to improve screening and referral processes is timely and essential. Plain Language Summary: There are many factors that contribute to low adult enrollment in cancer clinical trials, but previous research has indicated that provider and institutional barriers are the largest contributors to low cancer clinical trial enrollment.In this survey, we sought to gain insight into cancer clinical trial enrollment practices from the perspective of health care providers such as physicians and nurses. We found that only approximately half of respondents indicated their institution systematically screens their patients for clinical trials and this process is manual and time consuming. Furthermore, we found that providers infrequently search for and refer patients to clinical trials at other sites.Creating better screening methods could improve enrollment in clinical trials. A questionnaire was administered to understand provider perspectives and needs related to screening for cancer clinical trial eligibility, including assessment of incentives, barriers, and infrastructure related to opening and referring to trials. Findings from the survey suggest that automated screening tools built into clinical workflows could result in more frequent trial eligibility screening, especially for offsite trials. [ABSTRACT FROM AUTHOR]

Enrollment in cancer clinical trials cannot occur without first successfully identifying trials for which patients are a match based on their clinical characteristics. A lack of onsite matching trials has been identified as the single largest barrier preventing patients from participating in clinical trials. The site‐agnostic cancer clinical trial matching environment is a mix of public and private tools and infrastructure that are not designed to work together to facilitate trial matching in an efficient manner. To identify policy and infrastructure solutions that could enable more effective and more frequent use of third‐party site‐agnostic matching, the American Cancer Society Cancer Action Network held a summit to examine challenges and propose consensus recommendations that could address those challenges. At this 2019 summit, stakeholders in this field examined these barriers and challenges and made a number of policy and infrastructure recommendations to improve the ability of this environment to work in a more coordinated and efficient manner. Third‐party, site‐agnostic cancer clinical trial matching services hold the potential to help identify clinical trial opportunities for significantly more patients than are offered clinical trial participation via current onsite‐only trial eligibility screening. Fully leveraging the benefits of such services, however, will only be possible with improvements to this sector, and here a set of consensus recommendations are provided. [ABSTRACT FROM AUTHOR]

A lack of diversity amongst participants in cancer clinical trials has raised scrutiny over the past decade. Patients with limited English proficiency (LEP) are further excluded. One modifiable reason for low LEP participation is a lack of non-English consent forms. We queried the clinical trials registry database at an academic hospital serving a predominantly Spanish-speaking patient population. Clinical trials related to gynecology oncology were evaluated for the availability of fully translated Spanish consent forms, the racial and ethnic identification of enrolled patients, and the number of signed Spanish consents. Enrolment data was compared before and after 2019, when institutional financial support for document translation was withdrawn. Sixteen gynecologic oncology clinical trials were opened between 2014 and 2022, with 10 trials enrolling 128 patients. Eight trials opened prior to 2019, all with fully translated consent forms. Seven of these trials enrolled 99 participants, 70% of whom identified as Hispanic and 60% who signed a Spanish consent. Eight trials opened after 2019 and one had a fully translated consent form. Three of the trials enrolled 29 participants, with 10% of subjects identifying as Hispanic and none signing a Spanish consent form. There was a decrease in fully translated clinical trial consent forms for gynecologic oncology studies following the loss of subsidized translation services in our single institution with a predominantly LEP population. This correlated with a decrease in enrollment of Hispanic subjects. To increase enrollment of diverse participants, including those with LEP, simple actions such as fully translating consent forms would help maintain equity in research conduct and improve clinical outcomes through trial involvement. [Display omitted] • Patients with limited English proficiency are underrepresented in clinical trials. • The simple act of translating consent forms can help maintain equity in trial enrollment. • Research institutions and industry should provide financial support towards translation services. [ABSTRACT FROM AUTHOR]

Decentralized clinical trials (DCTs) are gaining momentum in clinical research as these studies can be executed remotely through telemedicine and mobile/local health-care providers. The COVID-19 pandemic has further accelerated advances and adoption in this area. In the past few years, there has been significant development and growth in the use of remote data that are electronically transmitted from a clinical trial (CT) participant, from outside the clinical setting, to a data repository. Such data may include laboratory data, safety data, or outcome measures reported by the participant, the clinician or the observer. Similarly, wearable health monitoring devices are being increasingly used in health-care and CT settings. Digital biomarkers, which can support continuous measurement of physiologic parameters outside the physical confines of the clinical environment, are also creating new and improved opportunities for patient care and biomedical research, enabling remote monitoring and DCTs. There are several benefits to using remote data capture, wearables, and digital biomarkers in clinical health-care research; however, several questions and challenges still need to be addressed. In an effort to understand the adoption of these technologies in DCTs, and the challenges therein, the authors of this workstream conducted an online survey of clinical research stakeholders across India and reviewed 80 responses. The review article summarizes the key findings from this online survey. [ABSTRACT FROM AUTHOR]

Background: For people with cognitive impairment, hospitalisation is challenging and associated with adverse events as well as negative outcomes resulting in a prolonged hospital stay. Person-centred care can improve the quality of care and the experience of people with cognitive impairment during hospitalisation. However, current care processes in German hospitals are rarely person-centred. To enable successful implementation of person-centred care on hospital wards, change agents within the interprofessional team are key. The aim of this study is to test the feasibility and initial effects of a newly developed complex person-centred care intervention for people with cognitive impairment provided by expanded practice nurses in acute care. Methods: We will conduct an exploratory non-randomised controlled clinical trial with accompanying process and cost evaluation with three intervention and three control wards at one university hospital. The person-centred care intervention consists of 14 components reflecting the activities of expanded practice nurses within the interprofessional team on the intervention wards. The intervention will be implemented over a six-month period and compared with optimised care on the control wards. We will include people aged 65 years and older with existing cognitive impairment and/or at risk of delirium. The estimated sample size is 720 participants. The primary outcome is length of hospital stay. Secondary outcomes include prevalence of delirium, prevalence of agitation, sleep quality, and person-centred care. We will collect patient level data at six time points (t1 admission, t2 day 3, t3 day 7, t4 day 14, t5 discharge, t6 30 days after discharge). For secondary outcomes at staff level, we will collect data before and after the intervention period. The process evaluation will examine degree and quality of implementation, mechanisms of change, and the context of the complex intervention. The economic evaluation will focus on costs from the hospital's perspective. Discussion: The ENROLE-acute study will provide insights into the effectiveness and underlying processes of a person-centred care intervention for people with cognitive impairment provided by expanded practice nurses on acute hospitals wards. Results may contribute to intervention refinement and evidence-based decision making. Trial registration: Current controlled trials: ISRCTN81391868. Date of registration: 12/06/2023. URL: https://doi.org/10.1186/ISRCTN81391868 [ABSTRACT FROM AUTHOR]

Monitoring of clinical trials is critical to the protection of human subjects and the conduct of high-quality research. Even though the adoption of risk-based monitoring (RBM) has been suggested for many years, the RBM approach has been less widespread than expected. Centralized monitoring is one of the RMB pillars, together with remote-site monitoring visits, reduced Source Data Verification (SDV) and Source Document Reviews (SDR). The COVID-19 pandemic promoted disruptions in the conduction of clinical trials, as on-site monitoring visits were adjourned. In this context, the transition to RBM by all actors involved in clinical trials has been encouraged. In order to ensure the highest quality of data within a COVID-19 clinical trial, a centralized monitoring tool alongside Case Report Forms (CRFs) and synchronous automated routines were developed at the clinical research platform, Fiocruz, Brazilian Ministry of Health. This paper describes how these tools were developed, their features, advantages, and limitations. The software codes, and the CRFs are available at the Fiocruz Data Repository for Research—Arca Dados, reaffirming Fiocruz's commitment to Open Science practices. [ABSTRACT FROM AUTHOR]

Abbreviations AA Alopecia areata FDA Food and Drug Administration NIH National Institute of Health US United States Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. To the Editor: Alopecia areata (AA) affects 2% of the US population and causes non-scarring hair loss [[1]]. The National Library of Medicine ClinicalTrials.gov database was queried in January 2023 to identify clinical trials investigating AA therapeutics (search term: "alopecia areata"). [Extracted from the article]

Purpose: Although HPV-positive and negative oropharyngeal cancers are two distinct diseases, Post-Therapeutic Surveillance (PTS) modalities are similar. Adjusting PTS strategies to HPV status will represent a massive practice change that raises the issue of its acceptability, by both physicians and patients. Methods: Two distinct surveys were designed and submitted, respectively, to HPV-positive patients and physicians (surgeons, radiation and medical oncologists) involved in head and neck cancer treatment. Results: 133 patients and 90 physicians have participated to the study. Most patients were reluctant to embrace new PTS options (remote consultations, nurse consultations and smart phone applications). However, 84% of patients would be favorable to use HPV Circulating DNA (HPV Ct DNA) measurement to guide surveillance modalities. 57% of physicians acknowledged that our current PTS strategy is improvable and most of them would accept the use of new monitoring options from the third year of follow-up. 87% of physicians would be interested to participate to a trial comparing the current PTS strategy to a new approach, where monitoring modalities (number of visits, imaging prescription) would depend on HPV Ct DNA level. Conclusions: Patients and physicians are aware that PTS modalities should depend on HPV status. Their adhesion is a prerequisite to any potential changes. Strategies based on HPV Ct DNA measurement should be assessed within a randomized clinical trial. [ABSTRACT FROM AUTHOR]

Management of low-risk ductal carcinoma in situ (DCIS) is controversial, with clinical trials currently assessing the safety of active monitoring amidst concern about overtreatment. Little is known about general community views regarding DCIS and its management. We aimed to explore women's understanding and views about low-risk DCIS and current and potential future management options. This mixed-method study involved qualitative focus groups and brief quantitative questionnaires. Participants were screening-aged (50–74 years) women, with diverse socioeconomic backgrounds and no personal history of breast cancer/DCIS, recruited from across metropolitan Sydney, Australia. Sessions incorporated an informative presentation interspersed with group discussions which were audio-recorded, transcribed and analysed thematically. Fifty-six women took part in six age-stratified focus groups. Prior awareness of DCIS was limited, however women developed reasonable understanding of DCIS and the relevant issues. Overall, women expressed substantial support for active monitoring being offered as a management approach for low-risk DCIS, and many were interested in participating in a hypothetical clinical trial. Although some women expressed concern that current management may sometimes represent overtreatment, there were mixed views about personally accepting monitoring. Women noted a number of important questions and considerations that would factor into their decision making. Our findings about women's perceptions of active monitoring for DCIS are timely while results of ongoing clinical trials of monitoring are awaited, and may inform clinicians and investigators designing future, similar trials. Exploration of offering well-informed patients the choice of non-surgical management of low-risk DCIS, even outside a clinical trial setting, may be warranted. [ABSTRACT FROM AUTHOR]

Introduction: Black Americans are disproportionately burdened by Alzheimer's disease (AD) relative to other racial groups in the United States and continue to be underrepresented in AD clinical trials. This review explores the primary barriers for participation in clinical trials among Black Americans and provides literature‐based recommendations to improve the inclusion of Black Americans in AD clinical trials. Methods: We searched electronic databases and gray literature for articles published in the United States through January 1, 2023, ultimately identifying 26 key articles for inclusion. Results: Barriers to participation in clinical trials for Black Americans are rooted in social determinants of health, including access to quality education and information, access to health care, economic stability, built environment, and community context. Best practices to improve the inclusion of Black Americans in clinical trials require pharmaceutical companies to adopt a multifaceted approach, investing in innovative strategies for site selection, development of local partnerships, outreach, and education. Discussion: While multisectoral action must occur to effectively address the disproportionate burden of AD on Black Americans, the pharmaceutical industry has an important part to play in this space due to their central role in product development and clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: Smoking is a global public health concern, with a significant negative impact on human health and healthcare spending. Vaping, or the use of electronic cigarettes (e-cigarettes), has emerged as a popular alternative to traditional nicotine replacement therapies (NRTs) for smoking cessation. While considered less harmful than combustible cigarettes, the long-term health effects of e-cigarettes (vaping) are unknown. Therefore, this study aimed to identify and provide a comprehensive overview of the performance of vaping in clinical trials.Patients and Methods: A search was conducted in the ClinicalTrials.gov database on April 14th, 2023, using the search term "smoking cessation, e-cigarettes, NRTs, and vaping". Inclusion and exclusion criteria were defined to identify relevant clinical trials. Randomized controlled trials (RCTs) and non-randomized clinical trials that evaluated vaping as a therapeutic approach to smoking cessation were included.Results: A total of 87 clinical trials were identified, of which only seven were related to smoking cessation through vaping as a form of treatment. The primary endpoint was the effect of vaping as smoking cessation, and the secondary endpoints were patients' abstinence rate, withdrawal symptoms, and adverse events of e-cigarettes. Most of the trials used e-cigarettes as an intervention, with some trials including a combination of e-cigarettes and other NRTs. The trials lasted from 4 weeks to 12 months. The overall results of the trials indicated that vaping was effective in helping smokers to quit. It was also associated with a lower risk of adverse events than combustible cigarettes.Conclusion: Vaping appears to be an effective method for smoking cessation, and it is associated with a lower risk of adverse events than combustible cigarettes. [ABSTRACT FROM AUTHOR]

Objective: Substantial disparities exist in clinical trial participation, which is problematic in diseases such as lupus that disproportionately affect racial/ethnic minority populations. Our objective was to examine the effectiveness of an online educational course aiming to train medical providers to refer Black and Latino patients to lupus clinical trials (LCTs). Methods: The American College of Rheumatology's Materials to Increase Minority Involvement in Clinical Trials (MIMICT) study used an online, randomized, 2‐group, pretest/posttest design with medical and nursing providers of multiple specialties. We exposed intervention group participants to an education course, while the control group participants received no intervention. Controlling for the effects of participant characteristics, including specialty, and professional experience with lupus, we modeled relationships among exposure to the education course and changes in knowledge, attitudes, self‐efficacy, and intentions to refer Black and Latino patients to LCTs. We also examined education course satisfaction. Results: Compared to the control group, the intervention group had significantly higher posttest scores for knowledge, self‐efficacy, and intentions to refer Black and Latino patients to LCTs. Both medical and nursing trained intervention group participants had significantly higher mean posttest scores for knowledge and intentions to refer compared to the medical and nursing trained control group participants. Attitude was insignificant in analysis. The online education course, which received a favorable summary score, indicated that satisfaction and intentions to refer were strongly and positively correlated. Conclusion: The MIMICT education course is an effective method to educate medical providers about LCTs and to improve their intentions to refer Black and Latino patients. [ABSTRACT FROM AUTHOR]

The article offers information on the transformative potential of artificial intelligence (AI) in science, medicine, and clinical research. Topics include the application of AI in clinical trials, particularly through natural language processing (NLP) models for event adjudication. The authors highlight the need for innovation in clinical research, given the growing costs and obstacles faced by the current clinical trials enterprise.

The effect of haemodynamic monitoring of pulmonary artery pressure has predominantly been studied in the USA. There is a clear need for randomised trial data from patients treated with contemporary guideline-directed-medical-therapy with long-term follow-up in a different health-care system. MONITOR-HF was an open-label, randomised trial, done in 25 centres in the Netherlands. Eligible patients had chronic heart failure of New York Heart Association class III and a previous heart failure hospitalisation, irrespective of ejection fraction. Patients were randomly assigned (1:1) to haemodynamic monitoring (CardioMEMS-HF system, Abbott Laboratories, Abbott Park, IL, USA) or standard care. All patients were scheduled to be seen by their clinician at 3 months and 6 months, and every 6 months thereafter, up to 48 months. The primary endpoint was the mean difference in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score at 12 months. All analyses were by intention-to-treat. This trial was prospectively registered under the clinical trial registration number NTR7673 (NL7430) on the International Clinical Trials Registry Platform. Between April 1, 2019, and Jan 14, 2022, we randomly assigned 348 patients to either the CardioMEMS-HF group (n=176 [51%]) or the control group (n=172 [49%]). The median age was 69 years (IQR 61–75) and median ejection fraction was 30% (23–40). The difference in mean change in KCCQ overall summary score at 12 months was 7·13 (95% CI 1·51–12·75; p=0·013) between groups (+7·05 in the CardioMEMS group, p=0·0014, and –0·08 in the standard care group, p=0·97). In the responder analysis, the odds ratio (OR) of an improvement of at least 5 points in KCCQ overall summary score was OR 1·69 (95% CI 1·01–2·83; p=0·046) and the OR of a deterioration of at least 5 points was 0·45 (0·26–0·77; p=0·0035) in the CardioMEMS-HF group compared with in the standard care group. The freedom of device-related or system-related complications and sensor failure were 97·7% and 98·8%, respectively. Haemodynamic monitoring substantially improved quality of life and reduced heart failure hospitalisations in patients with moderate-to-severe heart failure treated according to contemporary guidelines. These findings contribute to the aggregate evidence for this technology and might have implications for guideline recommendations and implementation of remote pulmonary artery pressure monitoring. The Dutch Ministry of Health, Health Care Institute (Zorginstituut), and Abbott Laboratories. [ABSTRACT FROM AUTHOR]

Aims: Source data verification (SDV) has been reported to account for up to 25% of the budget in clinical trials (CT) and cost‐benefit of SDV has been questioned. Guidelines for risk‐based monitoring (RBM) were published in 2013 by agencies and in 2016, ICH‐GCP‐E6‐(R2) added a requirement for risk‐based approaches. This report will perform a comparison of the impact of RBM vs classic monitoring (CM) on data quality (defined as accuracy of data reporting from source data to final trial data) and expected impact on costs of CTs. Methods: Data on residual errors from four, large comparable randomised CTs were examined by post‐trial SDV. Observed discrepancies were analysed in the categories of "overall" data, "major efficacy" and "major safety". In each category, the residual error rate was calculated as the number of discrepancies divided by the number of data‐fields verified. Results: A total of 1 716 087 data points were verified using CM and 323 174 using RBM. The overall error rate was 0.40% for RBM and 0.37% for CM (P < 0.01). For major efficacy, defined by risk assessment, the error rate was 0.15% and 0.28% (P < 0.0001); in major safety, defined by risk assessment, the error rate was 0.49% and 0.67% (P = 0.15), both in favour of the RBM approach. Conclusion: These empirical data, directly comparing RBM with CM, suggest that RBM improves data quality regarding data‐points of major importance to trial outcomes, efficacy and major safety. Overall, the RBM approach showed a correlation to reduced amount of data collection errors with major relevance for interpretation of study results and subject safety as well as reducing on‐site monitoring and data cleaning resources. [ABSTRACT FROM AUTHOR]

Clinical Trial Monitoring is the fundamental necessity to direct high-quality clinical research to guarantee research quality and subject protection according to regulatory standards. It is a sophisticated, innovation-based approach to utilizing a company's data, allowing for better-informed decisions regarding where and how to allocate resources. However, the monitoring plan is grouped into two kinds i.e., on-site and centralized monitoring. But recently, regulators have been urged to take on a risk-based monitoring system, as such sponsors are preferring centralized monitoring from the beginning of the trial. Risk-based monitoring assures the quality of trials by managing risks. Furthermore, the Food and Drug Administration (FDA) and European Medicine Agency (EMA) have embraced the risk-based approach and released a guideline paper on the subject. The FDA's proposed advice from 2013 discusses how to oversee clinical trials using a risk-based approach. Still, on-site monitoring, which is carried out by site visits, and centralized monitoring, which is carried out remotely or offsite, have their self-worth and advantages. Because of the greater complexity of grasping those monitoring procedures, in this review article, we will discuss both monitoring plans with an emphasis on centralized monitoring, which will aid in a better understanding of the entire in a nutshell. Also, we will emphasize the benefits, future, and implementation of Artificial Intelligence/Machine Learning in the risk-based monitoring strategy. [ABSTRACT FROM AUTHOR]

To conduct a content analysis of IRB webpages of select universities (academic health centers) in the USA that describe post IRB- approval monitoring activities. This was a qualitative study. Thematic analysis was the method to review the webpage content of selected academic health centers (AHC) within the USA. Some US academic health "centers" IRB administrative or research compliance offices conduct post- approval monitoring (PAM) of human subjects' research including clinical trials. The goals of this PAM programmes are to (a) ensure compliance to approved protocols, (b) preserve research integrity, (c) manage institutional risks, d) provide advisory/educational support to researchers, (e) recommend corrective actions for identified issues, and most importantly, (f) to protect the safety, rights, and well-being of research participants. Although not a requirement by law, the PAM program has legislative support in the US Code of Federal Regulations as part of the US Office for Human Research Protection's (OHRP) Federal Wide Assurance (FWA). This is especially for institutions that conduct studies funded by the Federal government. PAM on-site checks reveal various incidents of protocol deviations and violations. This includes issues with recruitment processes, informed consent discrepancies, and incidents of non-compliance. When a study protocol is identified as non-compliant, the principal investigator works with the PAM monitor to develop a corrective action plan that would allow the study to become compliant and avoid sanctions from the IRB or the regulatory authority. REC/IRB post-approval monitoring of clinical trials is a valuable mechanism of protection for research participants while giving educational and quality assurance support to researchers. The program enables early detection and resolution of non-compliance to approved protocols. The impact of the program in the USA requires further exploration. [ABSTRACT FROM AUTHOR]

Importance: Healthcare concepts for chronic diseases based on tele-monitoring have become increasingly important during COVID-19 pandemic. Objective: To study the effectiveness of a novel integrated care concept (NICC) that combines tele-monitoring with the support of a call centre in addition to guideline therapy for patients with atrial fibrillation, heart failure, or treatment-resistant hypertension. Design: A prospective, parallel-group, open-label, randomized, controlled trial. Setting: Between December 2017 and August 2019 at the Rostock University Medical Center (Germany). Participants: Including 960 patients with either atrial fibrillation, heart failure, or treatment-resistant hypertension. Interventions: Patients were randomized to either NICC (n = 478) or standard-of-care (SoC) (n = 482) in a 1:1 ratio. Patients in the NICC group received a combination of tele-monitoring and intensive follow-up and care through a call centre. Main outcomes and measures: Three primary endpoints were formulated: (1) composite of all-cause mortality, stroke, and myocardial infarction; (2) number of inpatient days; (3) the first plus cardiac decompensation, all measured at 12-months follow-up. Superiority was evaluated using a hierarchical multiple testing strategy for the 3 primary endpoints, where the first step is to test the second primary endpoint (hospitalization) at two-sided 5%-significance level. In case of a non-significant difference between the groups for the rate of hospitalization, the superiority of NICC over SoC is not shown. Results: The first primary endpoint occurred in 1.5% of NICC and 5.2% of SoC patients (OR: 3.3 [95%CI 1.4–8.3], p = 0.009). The number of inpatient treatment days did not differ significantly between both groups (p = 0.122). The third primary endpoint occurred in 3.6% of NICC and 8.1% of SoC patients (OR: 2.2 [95%CI 1.2–4.2], p = 0.016). Four patients died of all-cause death in the NICC and 23 in the SoC groups (OR: 4.4 [95%CI 1.6–12.6], p = 0.006). Based on the prespecified hierarchical statistical analysis protocol for multiple testing, the trial did not meet its primary outcome measure. Conclusions and relevance: Among patients with atrial fibrillation, heart failure, or treatment-resistant hypertension, the NICC approach was not superior over SoC, despite a significant reduction in all-cause mortality, stroke, myocardial infarction and cardiac decompensation. Trial registration ClinicalTrials.gov Identifier: NCT03317951. [ABSTRACT FROM AUTHOR]

The article discusses the reports the In the pharmaceutical sector, data from clinical trials is only being analyzed on a 20 percent scale. It highlights prospective advantages, including reducing costs, de-risking financial investments, and discovering proof of potential negative consequences. Additionally, it describes the efficiency of clinical trials, pharmacovigilance, and organizations and consortiums that support data integration and interoperability.

During recent years, the burden of bureaucracy in clinical research has increased dramatically, adversely impacting the activity of investigators and clinical research teams. Although compliance with the Declaration of Helsinki, the guidelines for Good Clinical Practice (GCP), and other applicable regulations remains unquestionable, their overinterpretation and substitution by the internal operating procedures of sponsors and Contract Research Organizations (CROs) have increased the administrative burden. A survey conducted by the European Society for Medical Oncology (ESMO) Clinical Research Observatory (ECRO) among 940 investigators confirmed that they considered that the administrative burden in clinical research is excessive; that administrative procedures could be reduced without affecting the safety and the rights of the patients and the quality of the data; and that bureaucracy represents an obstacle for clinical research. A panel of physicians with extensive experience in clinical research, composed by members of the ECRO and the ESMO Scientific Medical and Public Policy divisions, analyzed clinical trial procedures related to administrative workflow, pharmacovigilance, and medical care. The panel identified situations that generate debate between investigators and sponsors/CROs and selected real clinical scenarios that exemplify such situations. The panel discussed and proposed specific recommendations for those situations, based on GCP. This initiative aspires to streamline clinical research procedures and to become a platform for discussion among all clinical trial stakeholders, with the aim of promoting the sustainability of clinical research and the care of cancer patients. • The burden of bureaucracy in clinical research is overwhelming investigators and clinical research teams. • This ESMO manuscript proposes a framework of principles to improve sponsoring and monitoring of clinical trials. • We expect this awareness call to streamline clinical research and to promote the welfare of patients. [ABSTRACT FROM AUTHOR]

The article presents the discussion on remote patient monitoring has become critical to achieving better healthcare outcomes. Topics include technology allows for extended monitoring of patients' health parameters, such as vital signs, medication adherence, and symptom progression, without the need for frequent in-person visits; and wearables must align with the specific goals of the trial and uphold the highest standards of scientific rigor and validation.

The primary analysis in two‐arm clinical trials usually involves inference on a scalar treatment effect parameter; for example, depending on the outcome, the difference of treatment‐specific means, risk difference, risk ratio, or odds ratio. Most clinical trials are monitored for the possibility of early stopping. Because ordinarily the outcome on any given subject can be ascertained only after some time lag, at the time of an interim analysis, among the subjects already enrolled, the outcome is known for only a subset and is effectively censored for those who have not been enrolled sufficiently long for it to be observed. Typically, the interim analysis is based only on the data from subjects for whom the outcome has been ascertained. A goal of an interim analysis is to stop the trial as soon as the evidence is strong enough to do so, suggesting that the analysis ideally should make the most efficient use of all available data, thus including information on censoring as well as other baseline and time‐dependent covariates in a principled way. A general group sequential framework is proposed for clinical trials with a time‐lagged outcome. Treatment effect estimators that take account of censoring and incorporate covariate information at an interim analysis are derived using semiparametric theory and are demonstrated to lead to stronger evidence for early stopping than standard approaches. The associated test statistics are shown to have the independent increments structure, so that standard software can be used to obtain stopping boundaries. [ABSTRACT FROM AUTHOR]

JAMA: Journal of the American Medical Association has published a Special Communication titled "The Integration of Clinical Trials With the Practice of Medicine: Repairing a House Divided," which discusses the need to integrate clinical trials with clinical practice. The authors highlight the separate missions and infrastructures of clinical trialists and clinicians, leading to inefficiencies and limitations in trials. They propose solutions such as implementation science, novel statistical analysis approaches, and integration of trials with electronic health records. JAMA is launching a new series called "Integrating Clinical Trials and Practice" to explore innovations in trial design, funding, regulation, education, and application. The goal is to align clinical trials with clinical practice and improve patient care. [Extracted from the article]

Clinical trials are critical components of modern health care and infrastructure. Trials benefit society through scientific advancement and individual patients through trial participation. In fact, billions of dollars are spent annually in support of these benefits. Despite the massive investments, clinical trials often fail to accomplish their primary aims and trial enrollment rates remain low. Prior efforts to improve trial conduct and enrollment have had limited success, perhaps due to oversimplification of the complex, multilevel nature of trials. For these reasons, the authors propose applying implementation science to the clinical trials context. In this commentary, the authors posit clinical trials as complex, multilevel evidence-based interventions with significant societal and individual benefits yet with persistent gaps in implementation. An application of implementation science concepts to the clinical trials context as means to build common vocabulary and establish a platform for applying implementation science and practice to improve clinical trial conduct is introduced. Applying implementation science to the clinical trials context can augment improvement efforts and build capacity for better and more efficient evidence-based care for all patients and trial stakeholders throughout the clinical trials enterprise. [ABSTRACT FROM AUTHOR]

Clinical studies of rescue medications for seizure clusters are limited and are designed to satisfy regulatory requirements, which may not fully consider the needs of the diverse patient population that experiences seizure clusters or utilize rescue medication. The purpose of this narrative review is to examine the factors that contribute to, or may influence the quality of, seizure cluster research with a goal of improving clinical practice. We address five areas of unmet needs and provide advice for how they could enhance future trials of seizure cluster treatments. The topics addressed in this article are: (1) unaddressed end points to pursue in future studies, (2) roles for devices to enhance rescue medication clinical development programs, (3) tools to study seizure cluster prediction and prevention, (4) the value of other designs for seizure cluster studies, and (5) unique challenges of future trial paradigms for seizure clusters. By focusing on novel end points and technologies with value to patients, caregivers, and clinicians, data obtained from future studies can benefit the diverse patient population that experiences seizure clusters, providing more effective, appropriate care as well as alleviating demands on health care resources. [ABSTRACT FROM AUTHOR]

An innovative approach to patient management, evidence-based policy development, and clinical drug trials is required to provide personalized care and to improve the likelihood of finding an effective treatment for Motor Neurone Disease (MND). The MiNDAus Partnership builds on and extends existing national collaborations in a targeted approach to improve the standard and coordination of care for people living with MND in Australia, and to enhance the prospects of discovering a cure or treatment. Relationships have been developed between leading clinical and research groups as well as patient-centered organizations, care providers, and philanthropy with a shared vision. MiNDAus has established a corporate structure and meets at least biannually to decide on how best to progress research, drug development, and patient management. The key themes are; (i) empowering patients and their family carers to engage in self-management and ensure personalized service provision, treatment, and policy development, (ii) integration of data collection so as to better inform policy development, (iii) unifying patients and carers with advocacy groups, funding bodies, clinicians and academic institutions so as to inform policy development and research, (iv) coordination of research efforts and development of standardized national infrastructure for conducting innovative clinical MND trials that can be harmonized within Australia and with international trials consortia. Such a collaborative approach is required across stakeholders in order to develop innovative management guidelines, underpinned by necessary and evidence-based policy change recommendations, which, will ensure the best patient care until a cure is discovered. [ABSTRACT FROM AUTHOR]

Objectives: Plaque control by improved domestic oral hygiene is essential in periodontal treatment. However, changing treatment providers may interfere with building a dentist-patient relationship and in turn affect treatment success. The aim of this randomized, controlled, prospective short-term study was to determine the influence of either one or four different pre-graduate practitioners on patients' oral hygiene parameters during active periodontal therapy. Material and Methods: A total of 55 patients with periodontitis were allocated to two groups. Within the group "continuous treatment" (CT, n = 27), each patient was treated by one individual practitioner over the treatment period. For patients of the group "discontinuous treatment" (DT, n = 28), treatment in each session was performed by a different practitioner. Periodontal parameters (BOP, PBI, and PCR) were assessed at two timepoints: T1 (baseline) and T2 (end of active therapy). Results: With CT, the PBI improved in 93% of the patients, compared to 71% with DT (p = 0.048). T1-T2 intragroup analysis showed a statistically significant improvement of all observed clinical parameters with no differences in ∆PBI, ∆BOP, and ∆PCR. Spearman's correlation analysis revealed a weak correlation between PCR and BOP of CT only. Conclusions: In the present study, improvement of all parameters was comparable between the groups. PBI, as a parameter displaying patient's domestic plaque control compliance, improved in more patients from CT than DT. This is possibly indicating an advantage of continuous treatment by one single practitioner. Clinical relevance: Treatment by either a single practitioner or by multiple, constantly changing practitioners might influence patients' compliance to modify their behaviour when medically necessary. [ABSTRACT FROM AUTHOR]