Exercise oncology clinical trials during treatments: a commentary to address the safety concerns of human subjects regulatory reviewers and committees.

Exercise oncology clinical trials contribute to the advancement of our scientific knowledge and to the safety and care of patients diagnosed with cancer. Nevertheless, regulatory reviewers and committees may not be familiar with the well-documented long-term health benefits and safety of the regular practice of physical activity. Moreover, they may not see how the benefits outweigh the risks in the context where patients diagnosed with cancer are typically seen as vulnerable. Therefore, we would like to provide a purpose-built overview of exercise oncology clinical trials for members involved in institutional review committees, including the Scientific Review Committee (SRC), the Institutional Review Board (IRB), and the Data Safety Monitoring Committee (DSMC) to facilitate a greater understanding of the safety and benefits of physical activity during cancer treatments. Communication is key to improve the success of exercise oncology clinical trials, which are vital for patients diagnosed with cancer.

Xenograft recipients and the right to withdraw from a clinical trial.

Preclinical xenotransplantation research using genetically engineered pigs has begun to show some promising results and could one day offer a scalable means of addressing organ shortage. While it is a fundamental tenet of ethical human subject research that participants have a right to withdraw from research once enrolled, several scholars have argued that the right to withdraw from xenotransplant research should be suspended because of the public health risks posed by xenozoonotic transmission. Here, we present a comprehensive critical evaluation of the claim that xenotransplant recipients should be required to waive their right to withdraw from lifelong biosurveillance. We conclude that if xenotransplantation requires participants to waive their right to withdraw, then clinical trials may not be justifiable, given the ethical and legal obstacles involved with doing so. Consequently, if clinical trials are permitted with a right to withdraw, then they may pose a significant public health risk.

Standardized Extract of Valeriana officinalis Improves Overall Sleep Quality in Human Subjects with Sleep Complaints: A Randomized, Double-Blind, Placebo-Controlled, Clinical Study.

INTRODUCTION: Sleep deficit or poor sleep leads to ill-health, whereas sleep deprivation for longer periods of time increases the risk of developing adverse conditions associated with poor quality of life, and high socioeconomic impact. The treatments for sleep disturbances include melatonin and over-the-counter medicines like diphenhydramine and doxylamine, all of which have negative side effects. Valerian (Valeriana officinalis L.) is a traditional herb and the most preferred alternate sleep solution to manage sleep complaints. METHODS: Eighty adult subjects with sleep complaints were randomized in 1:1 ratio to receive either V. officinalis extract (VE) or placebo for 8 weeks in a double-blind, placebo-controlled, parallel, clinical study. Primary efficacy endpoints included the Pittsburgh Sleep Quality Index (PSQI) and sleep latency using wrist actigraphy (WA), as well as a number of secondary endpoints, including sleep parameters such as actual sleep time and sleep efficiency using WA, the Epworth Sleepiness Scale (ESS), the Beck Anxiety Inventory (BAI), the Visual Analogue Scale (VAS) for the feeling of waking up refreshed, and a tertiary endpoint of sleep parameters using polysomnography (PSG) in a subset of 20 subjects per group. Safety parameters included physical examination, vital sign measurements, hematology, and clinical chemistry tests. Adverse events and serious adverse events were monitored throughout the study period. RESULTS: Seventy-two subjects (35 and 37 subjects in the placebo and VE groups, respectively) completed the study and were included in the efficacy assessments. On Days 14, 28, and 56, the PSQI Total Score in the VE group decreased significantly (p < 0.05) compared to the placebo group. Further, the VE group showed significant improvements (p < 0.05) in sleep latency and actual sleep time on Days 3, 14, 28, and 56, and sleep efficiency on Days 14, 28, and 56, as evaluated by WA. There was a decrease (p < 0.05) in anxiety (BAI) on Days 14, 28, and 56, daytime drowsiness (ESS) on Days 28 and 56, and an increased feeling of waking up refreshed (VAS) on Days 28 and 56 compared to placebo. PSG results carried out in subset of subjects revealed significant improvements (p < 0.05) in total sleep time, sleep latency, and sleep efficiency on Day 56 in the VE group compared to the placebo group. No safety concerns were observed throughout the study. CONCLUSION: VE supplementation significantly improved various subjective and objective parameters of sleep in young subjects with mild insomnia symptoms, such as overall sleep quality, sleep latency, sleep efficiency, and total sleep time. We also observed decreased anxiety and daytime sleepiness, and improved feeling of being refreshed after waking up with VE supplementation. VE was found to be safe and well tolerated throughout the study. TRIAL REGISTRATION: Clinical Trials Registry of India: CTRI/2022/05/042818.

Safety and efficacy of REGENDIL™ infused hair growth promoting product in adult human subject having hair fall complaints (alopecia).

BACKGROUND: Hair serum is recommended therapy for the management of hair fall problems. People of all ages suffer from hair fall. AIM: To evaluate safety and efficacy of hair growth promoting product in healthy adult subjects with hair fall complaints (Alopecia). METHODS: In this safety and efficacy clinical study, 32 healthy individuals (aged 18-45 years) experiencing hair loss were enrolled. Participants applied 0.5 mL of the product to the affected scalp area daily for 60 days. The study evaluated various factors, including hair growth rate, thickness, density, scalp condition using CASLite-Nova, anagen-to-telogen ratio, hair fall reduction, overall hair and scalp appearance, hair strength, and participants' subjective perceptions of the product. RESULTS: Highly statistically significant improvement was observed in hair growth rate, thickness, and density at Day 30 and Day 60. Hair growth rate increased (p-value <0.01) by 10.52% in 30 days and 31.62% in 60 days after test product application. Average hair growth increased by 424.21 µm/day and 487.31 µm/day at Day 30 and 60 respectively. The hair growth improved by up to 1.5 times after 60 days of usage in healthy subjects with hair fall complaints. No adverse events or product-related adverse events were reported. CONCLUSION: Hair serum containing REGENDIL™ (Redensyl, AnaGain, Procapil, Capilia longa), and 5 kDa hyaluronic acid was efficacious and well tolerable in reducing hair fall (Alopecia). Hair serum significantly improved hair growth, hair density, hair thickness, and hair strength within 60 days of usage, thereby demonstrating it worth as a beneficial inclusion as a daily haircare product.

An Overview of Data Management in Human Subjects Research.

Research studies generate data in various forms. Data can be quantitative or qualitative. Research involving human subjects requires protection of data to ensure privacy. Various regulations and local policies need to be followed to ensure data security. Data management plans are critical for effective data stewardship and include details plan on data collection, management, storage, and formatting. This paper will review data collection tools, data security strategies, file management, data storage, government regulations, prepping data for analysis, reference management, and file management.

Controls, comparator arms, and designs for critical care comparative effectiveness research: It's complicated.

BACKGROUND: Comparative effectiveness research is meant to determine which commonly employed medical interventions are most beneficial, least harmful, and/or most costly in a real-world setting. While the objectives for comparative effectiveness research are clear, the field has failed to develop either a uniform definition of comparative effectiveness research or an appropriate set of recommendations to provide standards for the design of critical care comparative effectiveness research trials, spurring controversy in recent years. The insertion of non-representative control and/or comparator arm subjects into critical care comparative effectiveness research trials can threaten trial subjects' safety. Nonetheless, the broader scientific community does not always appreciate the importance of defining and maintaining critical care practices during a trial, especially when vulnerable, critically ill populations are studied. Consequently, critical care comparative effectiveness research trials sometimes lack properly constructed control or active comparator arms altogether and/or suffer from the inclusion of "unusual critical care" that may adversely affect groups enrolled in one or more arms. This oversight has led to critical care comparative effectiveness research trial designs that impair informed consent, confound interpretation of trial results, and increase the risk of harm for trial participants. METHODS/EXAMPLES: We propose a novel approach to performing critical care comparative effectiveness research trials that mandates the documentation of critical care practices prior to trial initiation. We also classify the most common types of critical care comparative effectiveness research trials, as well as the most frequent errors in trial design. We present examples of these design flaws drawn from past and recently published trials as well as examples of trials that avoided those errors. Finally, we summarize strategies employed successfully in well-designed trials, in hopes of suggesting a comprehensive standard for the field. CONCLUSION: Flawed critical care comparative effectiveness research trial designs can lead to unsound trial conclusions, compromise informed consent, and increase risks to research subjects, undermining the major goal of comparative effectiveness research: to inform current practice. Well-constructed control and comparator arms comprise indispensable elements of critical care comparative effectiveness research trials, key to improving the trials' safety and to generating trial results likely to improve patient outcomes in clinical practice.

Patient participation in research projects in Community Pharmacies: An exploratory study

Introducción: En los últimos años ha habido un incremento de la participación de farmacias comunitarias en proyectos de investigación. El reclutamiento de pacientes juega un papel clave en el éxito de las investigaciones. Se han identificado barreras y facilitadores que promueven dicho reclutamiento por parte de los farmacéuticos, pero poco es sabido sobre la influencia de factores relacionados con los proyectos de investigación. El objetivo de este trabajo es observar la participación en diferentes investigaciones llevadas a cabo en farmacias comunitarias e identificar las variables propias de los estudios que puedan estar asociadas con la participación.Método: Se realizó un estudio multicéntrico experimental en 12 farmacias comunitarias que formaron parte de 4 proyectos de investigación. Se registró el número de pacientes que aceptaron/rechazaron participar. Se recogieron variables relacionadas con el estudio ofrecido y las farmacias. Se realizó un análisis bivariante mediante la prueba Chi-Cuadrado de Pearson y un análisis de los riesgos.Resultados: La participación total fue del 90,44 % (n=558). El tipo de estudio (OR=2,64; 95 %IC=1,47-4,75; trans-versal vs pragmático), el tipo de medida aplicada (OR=2,47; 95 %IC=1,43-4,36), la aplicación de zona de atención personalizada (ZAP) (OR=2,49; 95 %IC=1,44-4,39), y la solicitud de datos personales (OR=2,53; 95 %CI=1,47-4,42) mostraron asociación con la participación en los PI (p<0,05).Conclusiones: La participación por parte de los pacientes en proyectos de investigación es elevado y parece de-pender de factores propios del estudio aplicado. (AU)

Introduction: Over the last years there has been an increase in community pharmacy participation in research projects. Patient recruitment plays a key role in the research project success. Pharmacists’ barriers and enablers of recruitment have been identified, but little is known about the influence of research project-related factors. The aim of this paper is to explore patient participation in different studies conducted in community pharmacies and to identify study-specific factors that may be associated with it.Method: An experimental multicenter study was performed in 12 community pharmacies participating in 4 research projects. The number of patients who accepted/refused to participate was recorded. Variables related to each of-fered study and the project were collected. A bivariate analysis using Pearson’s Chi-Square test and a risk analysis were performed.Results: Participation rate was 90.44 % (n=558). Study type (OR=2.64; 95 % CI=1.47-4.75; cross-sectional vs prag-matic), the type of measurement applied (OR=2.47; 95 % CI=1.43-4.36), the use of a personalized care area (PCA) (OR=2.49; 95 % CI=1.44-4.39), and personal data request (OR=2.53; 95 %CI=1.47-4.42) showed association with par-ticipation in the RP (p<0.05).Conclusions: Patient participation in research projects is high and appears to rely on study-specific factors. (AU)

[The "Ethical Guidelines for Medical and Biological Research Involving Human Subjects" and the "Act on the Protection of Personal Information"-Revisions in 2022 and 2023, Expectations, and Challenges].

The relationship between the" Act on the Protection of Personal Information" and the" Ethical Guidelines for Medical and Biological Research Involving Human Subjects" will be explained, along with their respective revisions. It is highly desirable to consider and develop Japanese regulations that allow researchers to devote more time to their research.

Racial and gender disparities in traumatic brain injury clinical trial enrollment.

OBJECTIVE: Despite the increasing number of women and racial/ethnic minorities sustaining traumatic brain injuries (TBIs), they are underrepresented in TBI clinical trials. This study aimed to evaluate gender and racial diversity in enrolled cohorts of TBI clinical trials to identify trends and predictors of increased disparity over time. METHODS: The authors reviewed TBI clinical trials with reported results registered on the website ClinicalTrials.gov between 2008 and 2022. The studies were assessed for the proportion of women and racial/ethnic minorities enrolled as well as their reporting of race- and gender-specific characteristics such as gender ratio (GR) and Racial Diversity Index (RDI). Further study parameters, including year and duration, phase, trial design, type of funding, and trial completion, were also included. RESULTS: One hundred thirty-five clinical trials met inclusion criteria, of which 65 and 134 reported race and gender, respectively. Twenty-five trials were found to have existing racial disparity (RDI < 1). Comparatively, industry-funded trials had a 26% greater likelihood of racial disparities (p = 0.026), whereas federally funded trials were 30% less likely to demonstrate racial disparities (p = 0.031). Sixty-six trials had gender disparities (GR < 0.4) present, with federally funded trials showing 37.1% greater rates of gender disparity (p < 0.001, adjusted OR 5.47, 95% CI 2.26-14.25). The impact of funding source on race and gender remained significant despite adjusting for other covariates in the multivariate analyses. Racial disparity was negatively correlated with trial completion rate (p < 0.001). Disparities were not found to improve over the 14-year time span. CONCLUSIONS: Racial and gender disparities in TBI clinical trial enrollment persist, and the lack of diversity may lead to biased evidence-based medicine. Efforts should be made to increase the representation of women and racial/ethnic minorities in TBI clinical trials to ensure equitable access to effective treatments for all populations.

Analysis of the concurrent validity and reliability of five common clinical goniometric devices.

Measurement errors play an important role in the development of goniometric equipment, devices used to measure range of motion. Reasonable validity and reliability are critical for both the device and examiner before and after to testing in human subjects. The objective is to evaluate the concurrent validity and reliability of five different clinical goniometric devices for the purpose of establishing an acceptable measurement error margin for a novel device. We explored the validity and inter- and intrarater reliability scores of five goniometric devices namely (i) the universal goniometer (UG), a two-armed hand-held goniometer, (ii) the inclinometer (IC), featuring a single base, fluid level, and gravity-weighted inclinometer, (iii) the digital inclinometer (DI), functioning as both a DI and dynamometer, (iv) the smartphone application (SA), employing gyroscope-based technology within a smartphone platform application and (v) the modified inclinometer (MI), a gravity pendulum-based inclinometer equipped with a specialized fixing apparatus. Measurements were obtained at 12 standard angles and 8 human shoulder flexion angles ranging from 0° to 180°. Over two testing sessions, 120 standardized angle measurements and 160 shoulder angle measurements from 20 shoulders were repetitively taken by three examiners for each device. The intraclass correlation coefficient (ICC), standard error of measurement (SEM), and minimal detectable change (MDC) were calculated to assess reliability and validity. Concurrent validity was also evaluated through the execution of the 95% limit of agreement (95% LOA) and Bland-Altman plots, with comparisons made to the UG. The concurrent validity for all device pairs was excellent in both study phases (ICC > 0.99, 95% LOA - 4.11° to 4.04° for standard angles, and - 10.98° to 11.36° for human joint angles). Inter- and intrarater reliability scores for standard angles were excellent across all devices (ICC > 0.98, SEM 0.59°-1.75°, MDC 1°-4°), with DI showing superior reliability. For human joint angles, device reliability ranged from moderate to excellent (ICC 0.697-0.975, SEM 1.93°-4.64°, MDC 5°-11° for inter-rater reliability; ICC 0.660-0.996, SEM 0.77°-4.06°, MDC 2°-9° for intra-rater reliability), with SA demonstrating superior reliability. Wider angle measurement however resulted in reduced device reliability. In conclusion, our study demonstrates that it is essential to assess measurement errors independently for standard and human joint angles. The DI is the preferred reference for standard angle testing, while the SA is recommended for human joint angle testing. Separate evaluations across the complete 0°-180° range offer valuable insights.

Comparison of thoracolumbar spine kinematics and injuries in reclined frontal impact sled tests between mid-size adult female and male PMHS.

Disparities in injury tolerance and kinematic response remain understudied despite field data highlighting sex-based differences in injury risk. Furthermore, the automotive industry anticipates occupants will prefer reclined seating in highly automated vehicles. This study aimed to compare thoracolumbar spine kinematics and injuries between mid-size female and male post-mortem human subjects (PMHS) in reclined frontal impacts. Seven adult PMHS (three female, four male) were tested in reclined (50°) 50 km/h frontal impacts. The PMHS were seated on a semi-rigid seat and restrained by a prototype three-point seat belt system designed to mitigate submarining. The 3-D motions of five vertebrae and the pelvis were measured by an optical motion tracking system. Pressure transducers were inserted into intervertebral discs at three locations along the lumbar spine to track timing of lumbar vertebra fractures. Due to variations in the geometry of the pelvis and soft tissue surrounding the pelvis compared to the male subjects, the female subjects could not be positioned in the seat the same as the males, and, as a result, the females and their belt anchors needed to be translated forward in the seat to maintain similar belt geometry relative to the males. The females exhibited similar pre-test spinal curvatures and kinematics to the males. An L1 fracture was observed in one of three female subjects and two of four male subjects, and timing of these fractures were both similar (61 âˆ¼ 65 ms) and close to the time of peak downward seat force. Generally, the female and male subjects exhibited similar kinematic and injury responses in this reclined frontal impact sled test condition.

Ethically cleared to launch?

Rules are needed for human research in commercial spaceflight.

"Dogs on Call": A Community-Engaged Human Subjects Training with Hospital Based Therapy Dog Teams.

Problem: As community-engaged research (CER) methods evolve, Institutional Review Boards (IRBs) must adapt policies to facilitate CER research. This paper describes a novel collaboration between hospital-based therapy dog volunteer teams (CERs), academic faculty, and an IRB. Subjects: CER volunteers delivered a canine-assisted intervention to hospitalized adults in a clinical trial. Methods: IRB members and faculty developed a human subjects protections training tailored to the volunteer handlers' role as study interventionists including an interactive video- and discussion-based training with a knowledge assessment. Findings: Fourteen volunteer handlers were trained. The expedited IRB review period was similar to national average rates (18 days.) Volunteer handlers have conducted 107 research visits with little patient attrition. Conclusion: Tailored human subjects trainings facilitate research with interventions delivered by people who are not typically involved in research. Bespoke CER human subjects training requires collaboration between researchers and IRBs and flexibility in IRB policy regarding CER.

A response to Al et al. Trials 2023;24:233.

In their recent paper, Al and colleagues (Trials 2023;24:233) argue that manipulation of the methods of recruitment using well-known techniques in order to increase enrollment can be ethically acceptable. This brief response challenges that notion as an affront to voluntariness and a devolution of the ethics of human subjects research to the "ethics" of the marketplace.

Recruitment of Young Adults: Lessons Learned From Research on Rural E-Cigarette Use and Cessation.

Electronic nicotine delivery system (ENDS) use continues to grow in rural areas of the United States. In particular, young adults (18-24 years) in rural areas are a hard-to-reach population in regard to understanding the growing ENDS use trend. The purpose of this article was to describe recruitment strategies that were used for a series of ENDS-relevant projects for young adults in rural areas, report recruitment yields from these strategies, and provide methodological considerations to aid researchers in improving recruitment. We used descriptive statistical methods to characterize recruitment yields (responses to screening vs initial invites, and number of individuals who fully met eligibility criteria vs responses to screening) from 2 ENDS studies that focused on 3 main recruitment strategies, including student directories, leadership offices (eg, Student Affairs), and regional tobacco control support networks (eg, Area Health Education Centers) for reaching young adults in rural communities. The recruitment yield rates varied and ranged from 2% to 14% depending on strategy with leadership offices resulting in the highest recruitment yield. Methodological considerations by strategy are described in detail. Results of this study can be used to inform tailored recruitment strategies to increase the representation of rural young adults in ENDS or other tobacco research.

Human Subjects Research Guidelines for Undergraduate Researchers: An Analysis of Institutional Review Board (IRB) Websites at Top Liberal Arts Colleges in the United States.

Teaching students about the ethics of Human Subject Research (HSR) should be a fundamental component of students' education about research. In this article, we analyze the Institutional Review Board (IRB) websites of top-ranked Liberal Arts Colleges (LACs) to examine their framing of HSR carried out by undergraduate students. Our descriptive quantitative analysis from 50 top-ranked LACs in the United States indicates that a majority of IRB websites provide information about undergraduate research, and most include information about students' classroom-based research. Our qualitative content analysis of a subsample of ten colleges' IRB websites provides information on how they inform and educate about issues including informed consent and highlight different resources for students including their research advisor, and disciplinary standards. We conclude by discussing recommendations for IRBs in their accessibility to undergraduates.

Global Health Perspectives on Race in Research: Neocolonial Extraction and Local Marginalization.

Best practices in global health training prioritize leadership and engagement from investigators from low- and middle-income countries (LMICs), along with conscientious community consultation and research that benefits local participants and autochthonous communities. However, well into the 20th century, international research and clinical care remain rife with paternalism, extractive practices, and racist ideation, with race presumed to explain vulnerability or protection from various diseases, despite scientific evidence for far more precise mechanisms for infectious disease. We highlight experiences in global research on health and illness among indigenous populations in LMICs, seeking to clarify what is both scientifically essential and ethically desirable in research with human subjects; we apply a critical view towards race and racism as historically distorting elements that must be acknowledged and overcome.