Participation In Clinical Studies Research Articles

Derivatization-free determination of chiral plasma pharmacokinetics of MDMA and its enantiomers

3,4-Methylenedioxymethamphetamine (MDMA) is an entactogen with therapeutic potential. The two enantiomers of MDMA differ regarding their pharmacokinetics and pharmacodynamics but the chiral pharmacology of MDMA needs further study in clinical trials. Here, an achiral and an enantioselective high performance liquid chromatography–tandem mass spectrometry method for the quantification of MDMA and its psychoactive phase I metabolite 3,4-methylenedioxyamphetamine (MDA) in human plasma were developed and validated. The analytes were detected by positive electrospray ionization followed by multiple reaction monitoring. The calibration range was 0.5–500 ng/mL for the achiral analysis of both analytes, 0.5–1,000 ng/mL for chiral MDMA analysis, and 1–1,000 ng/mL for chiral MDA analysis. Accuracy, precision, selectivity, and sensitivity of both bioanalytical methods were in accordance with regulatory guidelines. Furthermore, accuracy and precision of the enantioselective method were maintained when racemic calibrations were used to measure quality control samples containing only one of the enantiomers. Likewise, enantiomeric calibrations could be used to reliably quantify enantiomers in racemic samples. The achiral and enantioselective methods were employed to assess pharmacokinetic parameters in clinical study participants treated with racemic MDMA or one of its enantiomers. The pharmacokinetic parameters assessed with both bioanalytical methods were comparable. In conclusion, the enantioselective method is useful for the simultaneous quantification of both enantiomers in subjects treated with racemic MDMA. However, as MDMA and MDA do not undergo chiral inversion, enantioselective separation is not necessary in subjects treated with only one of the enantiomers.

Lessons Learned From Clinical Studies in Centronuclear Myopathies: The Patient Perspective—A Qualitative Study

BackgroundSince 2014, several clinical studies focusing on centronuclear myopathies have been conducted, including a prospective natural history study, a gene transfer clinical trial and a clinical trial using an antisense oligonucleotide. Dedicated patient organizations have played an important role in this process. The experience of members of these organizations, either as a study participant, parent or as a patient organization member communicating with the sponsors are potentially very informative for future trial design. MethodsWe investigated the burden of and the lessons learned from the first natural history studies and clinical trials from a patient perspective using a qualitative approach. We arranged 4 focus groups with a total of 37 participants from 3 large international patient organizations: ZNM-ZusammenStark!, the Myotubular Trust, and the MTM-CNM Family Connection. 4 themes, based on a systematic literature search were discussed: Expectations and preparation, Clinical study participation, Communication and Recommendations for future clinical trials. The focus group recordings were transcribed, anonymized, and uploaded to Atlas-ti version 8.1 software. The data were analyzed using a thematic content analysis. ResultsOverall, participants were realistic in their expectations, hoping for small improvements of function and quality of life. The realization that trial participation does not equate to a treatment was challenging. Participating in a clinical study had a huge impact on many aspects of daily life, both for patients and their immediate families. First-hand insights into the burden of the design and its possible effect on performance were provided, resulting in numerous compelling recommendations for future clinical studies. Furthermore, participants stressed the importance of clear communication, which was considered to be especially vital in cases of severe adverse events. Finally, while patients were understanding of the importance of adhering to the regulations of good clinical practice, they indicated that they would strongly appreciate a greater understanding and/or acknowledgment of the patient perspective and a reflection of this perspective in future clinical trial design. ConclusionThe acknowledgment and inclusion of patients’ perspectives and efficient and effective communication is expected to improve patient recruitment and retention in future clinical studies, as well as more accurate assessment of the patient performance related to suitable planning of the study visits.

Parental perspectives on pediatric inflammatory bowel disease: Unraveling concerns, and study participation willingness.

The impact of disease burden extends beyond pediatric inflammatory bowel disease (IBD) patients to include their parents. Previous studies, predating the biologic era, have highlighted parental concerns about potential side effects associated with IBD medications. However, there is a notable gap in the literature regarding parents' perceptions of clinical studies involving pediatric IBD patients. This study aims to explore the specific concerns troubling parents of children with IBD, identifying factors influencing these concerns, and assesses parental willingness to allow their child's participation in clinical studies. Utilizing social media, we disseminated an anonymous questionnaire to parents of pediatric IBD patients. The questionnaire encompassed queries about parental willingness for their child to partake in clinical studies, aspects of the disease deemed bothersome, and the sense of coherence scale (SOC). Responses were obtained from 101 parents, with a mean age of 46.4, of whom 82.2% were female. Concerns about potential future side effects of their child's medications surpassed worries about disease symptoms (80.04% vs. 73.47%). Linear regression analysis revealed that parents with lower SOC scores, limited medical care accessibility, and a higher age of the child at diagnosis, exhibited heightened concerns about the future impact of the disease on their child (p = 0.016, 0.003, and 0.045, respectively). While a majority rejected participation in studies involving new medications (54.5%), there was greater agreement for studies on nutritional therapies (84.2%) and complementary medicine (91.1%). Classification tree analysis indicated that women were more inclined to permit their child's participation in studies focusing on complementary medicine (adjusted p = 0.002). Parents of IBD patients express greater apprehension about potential side effects from IBD medications and display reluctance toward their child participating in clinical studies related to medications.

Identification of Persons Living with Dementia Using the Electronic Health Record

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) are underdiagnosed in the primary care setting. Proactive screening for cognitive impairment and subsequent evaluation and diagnosis of patients who screen positive are not routinely and reliably performed. As a result, identification of persons living with dementia (PLWD) for enrollment in clinical programs, clinical trials, and research studies can be challenging. The electronic health record (EHR) represents a potentially viable tool to efficiently and accurate identify PLWD.MethodsIn a large academic health care system in the U.S., we performed an EPIC EHR search for PLWD with the intent of enrolling them in an outpatient dementia care management program. The EHR algorithm used the following criteria for dementia: (1) an ICD‐10 dementia diagnosis in the problem list or past medical history or (2) an FDA‐approved drug on their active medication list. We performed chart review for patients who were identified to have potential dementia using this algorithm to confirm dementia diagnosis is documented in clinical notes.ResultsA total of 985 patients were identified by EHR criteria as potentially having dementia. After chart review, 747 (75.8%) were confirmed to have dementia documented in their clinical history and progress notes. One hundred thirty (13.2%) did not have a confirmed dementia diagnosis, 58 (5.9%) had an incomplete dementia evaluation, and 50 (5.0%) had only mild cognitive impairment. In addition, 55 (5.6%) were deceased.ConclusionWe found that an EHR algorithm can identify patients with dementia in a health plan population. This model may be a useful tool for a focused recruitment of potential participants in clinical trials, research studies, and clinical programs.

Post-Marketing Observational Study of the Safety and Efficacy of Fibrinogen Concentrate in Congenital Fibrinogen Deficiency in Patients of All Ages

Background and Significance: Congenital fibrinogen deficiency (CFD) is a rare coagulation disorder characterized by a lack or low levels of functional fibrinogen leading to inadequate clot formation. Patients with CFD may experience severe or frequent bleeding episodes (BEs), either spontaneously or following trauma or surgery. Human fibrinogen concentrate (HFC; Fibryga® [Octapharma]) can restore hemostasis, and its efficacy and safety has been demonstrated in interventional clinical studies of adult and pediatric patients. The primary objective of this planned observational study is to collect real-world evidence to further assess the safety profile of this HFC, in patients of all ages with congenital fibrinogen deficiency, by characterizing the risks of thrombosis and anaphylaxis following its administration for treatment of bleeding (Figure 1). The observational data collected in this study will provide a more comprehensive safety profile of this HFC in patients of all ages following its marketing authorization. Study Design and Methods: FORMA-07 (NCT03793426) is a prospective, non-interventional, multicenter, observational, post-marketing study. Patients of all ages with a documented diagnosis of CFD (i.e., congenital afibrinogenemia or hypofibrinogenemia) requiring on demand HFC for BE treatment are eligible for inclusion (Table 1). Exclusion criteria include other coagulation disorders, history of anti-fibrinogen inhibitors, and participation in concurrent clinical studies. This study will examine a highly purified, plasma derived, double virus inactivated/eliminated, lyophilized HFC, which will be used according to individual country approval and labelling, and individually dosed as per the locally approved package insert. Independent ethical committee approval will be sought prior to study start and freely given, written informed consent obtained from all participants, or legal guardians in the case of pediatric patients. This study will be conducted in accordance with the ethical principles laid down in the Declaration of Helsinki. The primary endpoint is the incidence of thromboembolic adverse drug reactions (ADRs) . Serious ADRs, ADRs of special interest (including thromboembolic events and anaphylaxis), and thromboembolic monitoring using the Wells Score will be documented. Hemostatic efficacy will be assessed as a secondary endpoint by the study investigator using a robust 4-point objective scale from 2 to 24 hours following treatment. FORMA-07 is ongoing and actively enrolling patients of all ages with CFD. The study aims to enroll ~25 patients over 7 years, collecting data from 105 BEs (≥10 major BEs in 10 patients). Results of HFC safety and efficacy will be continually monitored throughout the study. Completion is expected Q4 2027.

Examining Racial Disparities in Multiple Myeloma Research and Treatment

Multiple myeloma (MM) is a disease which occurs in all races, geographic locations, and ethnicities, however the burden of this cancer is especially prominent in the African American/Black population with prevalence estimated to be as high as two to three times that of the White population. As a result MM is the most common hematological malignancy in Black patients. Despite a higher disease burden, this population suffers disproportionate rates of mortality. From 2017-2022 Black men had a 6% higher incidence rate than White men, but a 19% higher mortality rate. This disparity in outcomes between ethnic groups is likely multifactorial. Some explanations include novel therapy underutilization, or prevalence of comorbid conditions. It may also be attributable to biological differences, such as an increase rate of immunoglobin A disease, and an increased rate of chromosome 14 translocations. There may as a result be a heterogenous response to novel MM therapy. Unfortunately, clinical trial participation of Black patients has been significantly underrepresented. Studies that sought to analyze the results of novel therapy trials in this population found a trend towards decreased efficacy, however, were unable to reach significance due to insufficient study participation. We conducted a pooled analysis of interventional phase III clinical trials obtained from ClinicalTrials.gov data from 01/01/2000 to 12/31/2022. Studies who did not include racial/ethnicity data were excluded. There were 34 trials included in total that met this criteria and included in this analysis. There were 16,405 total enrolled patients analyzed. 13,618 (83.01%) were White, 1,255 (9.21%) were Asian, 777 (4.74%) were Black/African American, and 454 (2.7%) identified as Hispanic, with the remaining identified as other. Study participation was analyzed over time. Percentage of patients enrolled by year showed a negative correlation in Black/African Americans over the analyzed period. Our analysis suggests greater efforts need to be made to ensure the enrollment of a more diverse and representative MM population. Although this disease is roughly twice as prevalent in Black populations, clinical trial study participation since 2003 involved 18-times more White than Black patients. Despite ongoing recognition of this problem, study participation in MM has continued to remain largely homogenous. Interventions that may improve this problem include fostering and rebuilding trust in the clinical trial system that was damaged from historical abuses, expanding clinical sites to more diverse areas, expanding/revising eligibility criteria, and employing changes to enrollment techniques that better represent the demographics of the population intended to treat. Ultimately, the clinical trials for an intervention should appropriately reflect the population who will use it, otherwise these novel treatments may have unexpected heterogeneity in efficacy and safety once employed clinically.

Mexican Americans agree to participate in longitudinal clinical research more than non-Hispanic whites

BackgroundThe National Institutes of Health has advocated for improved minority participation in clinical research, including clinical trials and observational epidemiologic studies since 1993. An understanding of Mexican Americans (MAs) participation in clinical research is important for tailoring recruitment strategies and enrollment techniques for MAs. However, contemporary data on MA participation in observational clinical stroke studies are rare. We examined differences between Mexican Americans (MAs) and non-Hispanic whites (NHWs) participation in a population-based stroke study.MethodsWe included 3,594 first ever stroke patients (57.7% MAs, 48.7% women, median [IQR] age 68 [58–79]) from the Brain Attack Surveillance in Corpus Christi Project, 2009–2020 in Texas, USA, who were approached and invited to participate in a structured baseline interview. We defined participation as completing a baseline interview by patient or proxy. We used log-binomial models adjusting for prespecified potential confounders to estimate prevalence ratios (PR) of participation comparing MAs with NHWs. We tested interactions of ethnicity with age or sex to examine potential effect modification in the ethnic differences in participation. We also included an interaction between year and ethnicity to examine ethnic-specific temporal trends in participation.ResultsBaseline participation was 77.0% in MAs and 64.2% in NHWs (Prevalence Ratio [PR] 1.20; 95% CI, 1.14–1.25). The ethnic difference remained after multivariable adjustment (1.17; 1.12–1.23), with no evidence of significant effect modification by age or sex (Pinteraction by age = 0.68, Pinteraction by sex = 0.83). Participation increased over time for both ethnic groups (Ptrend < 0.0001), but the differences in participation between MAs and NHWs remained significantly different throughout the 11-year time period.ConclusionMAs were persistently more likely to participate in a population-based stroke study in a predominantly MA community despite limited outreach efforts towards MAs during study enrollment. This finding holds hope for future research studies to be inclusive of the MA population.

Operation Diversify Plastic Surgery: An Innovative Strategy to Increase Diversity in Plastic and Reconstructive Surgery.

Healthcare disparities remain a significant problem facing the US healthcare system with recent evidence of persistent racial and ethnic disparities especially among patients from minority backgrounds. Recent studies have documented advantages to a racially and ethnically diverse surgical workforce such as higher patient satisfaction scores, superior patient compliance with physician recommendations, and increased participation in clinical research studies by minority patients. In plastic and reconstructive surgery (PRS), there is a noted deficit among residents and faculty that come from ethnically underrepresented in medicine (URiM) backgrounds despite recent efforts to increase diversity in PRS surgeons. URiM medical students from three of the four historically Black medical universities organized to discuss pathways to PRS. Operation Diversify Plastic Surgery is a student-led organization that was developed to address the lack of diversity in PRS, challenges faced by students from institutions that lack PRS residency training programs, and unique factors that affect URiM students interested in PRS. Available studies note that mentoring relationships and research opportunities were instrumental in recruiting URiM students into PRS residency programs. Operation Diversify Plastic Surgery is an innovative solution to the insufficient URiM PRS residency candidate pool by increasing medical student exposure to PRS via educational lectures, virtual mentoring opportunities, and insights into research fellowships.

Screening and validation of differentially expressed genes in adipose tissue of patients with obesity and type 2 diabetes mellitus.

White adipose tissue (WAT) plays a pivotal role in the onset of type 2 diabetes mellitus (T2DM) and obesity. Despite its significance the underlying pathogenesis and key genes associated with it remain elusive. In our study, we screened the differentially expressed genes (DEGs) in intra-abdominal WAT of T2DM patients with obesity, as well as those with simple obesity, aiming to lay a foundational theory for an in-depth investigation of T2DM pathogenesis and the identification of novel therapeutic targets. Gene expression datasets (GSE16415 and GSE71416) were retrieved from the Gene Expression Omnibus (GEO) database. We employed R for screening DEGs and conducted a functional enrichment analysis using the Metascape database. Combined Lasso regression and Boruta feature selection algorithms were used to identify key DEGs. Subsequently, these were cross-verified using the GSE29231 dataset. Samples and medical records were collected from clinical study participants. The mRNA and protein expressions of the key DEGs were verified using qRT-PCR and western blotting, respectively. We discerned a total of 130 DEGs, with 40 being upregulated and 90 downregulated. Functional and pathway enrichment analyses illuminated that these genes are instrumental in mediating metabolite and energy production, neutrophil-mediated immunity, and other associated biological processes. This includes their involvement in the tricarboxylic acid cycle, glycolysis/gluconeogenesis, peroxisome proliferator-activated receptors, and other signalling pathways. Two genes, CIDEA and FSCN1 emerged as key DEGs. The low expression of CIDEA and high expression of FSCN1 in the T2DM and obesity group were verified in clinical samples (P < 0.05). We established that CIDEA and FSCN1 manifest significant differential expression in T2DM patients who are obese. This suggests their potential as risk assessment markers and therapeutic targets for T2DM.

A high-throughput test enables specific detection of hepatocellular carcinoma

High-throughput tests for early cancer detection can revolutionize public health and reduce cancer morbidity and mortality. Here we show a DNA methylation signature for hepatocellular carcinoma (HCC) detection in liquid biopsies, distinct from normal tissues and blood profiles. We developed a classifier using four CpG sites, validated in TCGA HCC data. A single F12 gene CpG site effectively differentiates HCC samples from other blood samples, normal tissues, and non-HCC tumors in TCGA and GEO data repositories. The markers were validated in a separate plasma sample dataset from HCC patients and controls. We designed a high-throughput assay using next-generation sequencing and multiplexing techniques, analyzing plasma samples from 554 clinical study participants, including HCC patients, non-HCC cancers, chronic hepatitis B, and healthy controls. HCC detection sensitivity was 84.5% at 95% specificity and 0.94 AUC. Implementing this assay for high-risk individuals could significantly decrease HCC morbidity and mortality.

Unsupervised [18F]Flortaucipir cutoffs for tau positivity and staging in Alzheimer’s disease

PurposeSeveral [18F]Flortaucipir cutoffs have been proposed for tau PET positivity (T+) in Alzheimer’s disease (AD), but none were data-driven. The aim of this study was to establish and validate unsupervised T+ cutoffs by applying Gaussian mixture models (GMM).MethodsAmyloid negative (A−) cognitively normal (CN) and amyloid positive (A+) AD-related dementia (ADRD) subjects from ADNI (n=269) were included. ADNI (n=475) and Geneva Memory Clinic (GMC) cohorts (n=98) were used for validation. GMM-based cutoffs were extracted for the temporal meta-ROI, and validated against previously published cutoffs and visual rating.ResultsGMM-based cutoffs classified less subjects as T+, mainly in the A− CN (<3.4% vs >28.5%) and A+ CN (<14.5% vs >42.9%) groups and showed higher agreement with visual rating (ICC=0.91 vs ICC<0.62) than published cutoffs.ConclusionWe provided reliable data-driven [18F]Flortaucipir cutoffs for in vivo T+ detection in AD. These cutoffs might be useful to select participants in clinical and research studies.

Representative enrolment of older adults in clinical trials: the time is now

Representative enrolment of older adults in clinical trials: the time is now

The MPRINT Hub Data, Model, Knowledge and Research Coordination Center: Bridging the gap in maternal-pediatric therapeutics research through data integration and pharmacometrics.

Maternal and pediatric populations have historically been considered "therapeutic orphans" due to their limited inclusion in clinical trials. Physiologic changes during pregnancy and lactation and growth and maturation of children alter pharmacokinetics (PK) and pharmacodynamics (PD) of drugs. Precision therapy in these populations requires knowledge of these effects. Efforts to enhance maternal and pediatric participation in clinical studies have increased over the past few decades. However, studies supporting precision therapeutics in these populations are often small and, in isolation, may have limited impact. Integration of data from various studies, for example through physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling or bioinformatics approaches, can augment the value of data from these studies, and help identify gaps in understanding. To catalyze research in maternal and pediatric precision therapeutics, the Obstetric and Pediatric Pharmacology and Therapeutics Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Maternal and Pediatric Precision in Therapeutics (MPRINT) Hub. Herein, we provide an overview of the status of maternal-pediatric therapeutics research and introduce the Indiana University-Ohio State University MPRINT Hub Data, Model, Knowledge and Research Coordination Center (DMKRCC), which aims to facilitate research in maternal and pediatric precision therapeutics through the integration and assessment of existing knowledge, supporting pharmacometrics and clinical trials design, development of new real-world evidence resources, educational initiatives, and building collaborations among public and private partners, including other NICHD-funded networks. By fostering use of existing data and resources, the DMKRCC will identify critical gaps in knowledge and support efforts to overcome these gaps to enhance maternal-pediatric precision therapeutics.

"There's not enough studies": Views of black breast and ovarian cancer patients on research participation.

Black breast and ovarian cancer patients are underrepresented in clinical cancer trials disproportionate to the prevalence of these cancers in Black females. Historically, lower enrollment has been attributed to individualized factors, including medical mistrust, but more recently structural factors, including systemic racism, have received additional scrutiny. We interviewed Black women with a personal or family history of breast and ovarian cancer to understand their views and experiences related to research participation. Qualitative interviews were conducted via telephone or video conference and transcribed verbatim. Transcripts were qualitatively analyzed for iterative themes related to the offer and participation in cancer clinical trials and research studies, impact on cancer care, and recommendations to increase enrollment of Black patients. Sixty-one Black women completed an interview. Participants expressed that Black women are underrepresented in cancer research, and that this negatively impacted their own care. Many cited past historical abuses, including the Tuskegee syphilis trial, as a potential factor for lower enrollment but suggested that lower enrollment was better understood in the context of the entirety of their healthcare experiences, including present-day examples of patient mistreatment or dismissal. Participants suggested that proactive community engagement, transparency, and increased representation of Black research team members were strategies likely to foster trust and bolster research participation. Medical mistrust is only a partial factor in the lower participation of Black patients in cancer research. Researchers should implement the strategies identified by our participants to promote diverse enrollment and ensure that Black patients are included in future therapeutic advances.

Gene Therapy Drug Development for First-In-Human Study of Pediatric Diseases: Facilitating Change to Current Paradigms

Drug development in pediatrics is mandated under US and European Union legislation, and delays in pediatric studies can impact the appropriate labeling and use of therapeutics for children. Developing medical products for pediatrics is challenging, as there are several critical issues and factors to consider when initiating a pediatric drug development program. The International Conference Harmonisation guideline E11(R1) and criteria under 21 CFR part 50 subpart D define pediatric regulatory standards for drug developers and ensure the safety of pediatric participants in clinical studies. Adequate adult data are typically required before finalizing pediatric study designs and initiating pediatric studies by virtue of the Pediatric Research Equity Act. It is evolving that the Food and Drug Administration (FDA) is including adolescents in Phase 3 trials. In pediatrics, the lack of coordinated use of extrapolation for safety and efficacy amongst global regulatory agencies impacts the timelines and development of clinical trial designs. First-in-human pediatric trials may be justified if the aspects of 21 CFR 50, subpart D specifically 21 CFR 50.52 are addressed. For example, first-in-human pediatric gene therapy trials have been allowed in spinal muscular atrophy (SMA) using a benefit-risk assessment to justify the conduct of first-in-human trials in children. The statutory requirement to study children in clinical trials is influenced by the nature of the disease that is currently under study and needs to be personalized. These issues are addressed in this perspective on gene therapy treatment in children.

Social media advertising for clinical studies: Ethical and data protection implications of online targeting

Social media advertising has revolutionised the advertising world by providing data-driven targeting methods. One area where social media advertising is just gaining a foothold is in the recruitment of clinical study participants. Here, as everywhere, social media advertising promises more yield per money spent because the technology can better reach highly specialised groups. In this article, we point out severe societal risks posed by advertising for clinical studies on social media. We show that social media advertising for clinical studies in many cases violates the privacy of individual users (R1), creates collective privacy risks by helping platform companies train predictive models of medical information that can be applied to all their users (R2), exploits the weaknesses of existing guidelines in (biomedical) research ethics (R3) and is detrimental to the quality of (biomedical) research (R4). We argue that the well-intentioned promises, which are often associated with the use of social media advertising for clinical studies, are untenable from a balanced point of view. Consequently, we call for updates of research ethics guidelines and better regulation of Big Data and inferential analytics. We conclude that social media advertising – especially with vulnerable patient populations – is not suitable as a recruitment tool for clinical studies as long as the processing of (even anonymised) social media usage data and the training of predictive models by data analytics and artificial intelligence companies is not sufficiently regulated.

228. Infection Control Cluster Randomized Control Trials and Healthcare Facility Participation: A Need for Readiness Assessment

Abstract Background Validated tools to evaluate organizational readiness exist within the implementation science literature, but readiness assessments for healthcare organization participation in cluster randomized control trials (CRCTs) have not been developed. CRCTs have been important for increasing the evidence base for infection control. This study describes complex contextual factors that can impact participation in a multi-site infection control CRCTs within the VA healthcare system. Methods To assess study participation eligibility and feasibility, a survey of ten inpatient acute care patient units within five VA healthcare facilities was conducted to evaluate standard eligibility criteria such as facility and patient unit demographics, infection rates, and letters of support from leadership. With study delays we began conducting readiness evaluations through email communications and conference calls. We identified several metrics of readiness including competing priorities, identification of champions/ stakeholder engagement, and research infrastructure. Results Our Initial survey metrics received from facilities interested in study participation were efficient in detecting study eligibility but lacked efficiency to detect study feasibility. Later metrics identified barriers to feasible study implementation (i.e., readiness), primarily competing priorities, specifically due to the pandemic. Other barriers included the lack of research infrastructure and lack of champion identification/stakeholder engagement. These contextual factors were generally elicited through ongoing communication rather than from the initial survey assessment. Conclusion Organizational readiness can delay or impede important infection control CRCTs. This study exemplifies the complexity of healthcare organizations participation in clinical studies that may not be addressed in existing readiness tools or assessments. The emergence of the covid pandemic amplified the importance of identifying a wide range of contextual factors that need to be captured in ongoing assessments for readiness. An essential first step in developing organizational readiness tools and assessments is to identify and define readiness constructs in complex changing healthcare settings. Disclosures All Authors: No reported disclosures.

A Bayesian method for safety signal detection in ongoing blinded randomised controlled trials.

Sponsors have a responsibility to minimise risk to participants in clinical studies through safety monitoring. The FDA Final Rule for IND Safety Reporting requires routine aggregate safety evaluation, including in ongoing blinded studies. We are interested in estimating the probability that the true adverse event rate in the experimental arm exceeds that in the control arm. We developed a Bayesian approach that specifies an informative meta-analytic predictive prior on the event probability in the control arm and an uninformative prior on that in the experimental arm. We combined these priors with a mixture likelihood that considers each patient in the ongoing blinded study may belong to the experimental or control arm. This allowed us to estimate the quantity of interest without unblinding. We evaluated our method by simulation, pairing scenarios that differed only in whether a safety signal was present or missing, and quantifying the ability of our model to discriminate using signal detection theory. Our approach shows benefit. It detects safety signals more reliably with greater sample sizes and for common rather than rare events. Performance does not deteriorate markedly when historical studies exhibit heterogeneous hazards or non-constant hazards. Our method will allow us to monitor safety signals in ongoing blinded studies with the goal of earlier identification and risk mitigation. Our method could be adapted to use informative priors on both arms or predictive covariates where pertinent data exist. We stress that ongoing safety monitoring should involve a multi-disciplinary team where statistical methods are paired with medical judgement.

INVESTIGATING THE EFFECT OF INSPIRED OXYGEN FRACTION ON RIGHT VENTRICULAR 3D STRAIN DURING GENERAL ANAESTHESIA IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE.

<h3>Introduction</h3> Patients with coronary artery disease (CAD) undergoing general anesthesia are at risk of perioperative complications. Hyperoxia is a known coronary vasoconstrictor. However, it is also a pulmonary vasodilator, reducing right ventricular afterload. Thus, there may be competing effects of hyperoxia on right ventricular function. In this study we investigated the effects of hyperoxia and normoxia on right ventricular (RV) function assessed by 3D transesophageal echocardiography (TEE) during general anesthesia in CAD patients before elective coronary artery bypass graft surgery. <h3>Methods</h3> In this randomized clinical trial study participants (n=106) were prospectively recruited using a crossover design. In anesthetized patients the fraction of inspired oxygen (FiO2) was titrated to a normoxic state (FiO2=0.3) and a hyperoxic state (FiO2=0.8). At both states TEE images were acquired to assess RV ejection fraction (RVEF) and global longitudinal free-wall strain (RVGLS). <h3>Results</h3> There was no difference between normoxia and hyperoxia in RVEF (46±6% vs. 45±8, p=0.504) nor in RVGLS (-22.4±4.8 vs. -21.9±4.3, p=0.352). However, RV function improved and worsened in some patients. ROC analysis (Figure A) shows that RVGLS at normoxia can better predict, which patients will worsen with excess oxygen. With a cut-off of -20% for RVGLS (Sensitivity: 87%, Specificity: 49%), it was demonstrated that hyperoxia was beneficial for patients with a poor strain at normoxia (>-20%) but detrimental for those with normal strain at normoxia (<-20%, Figure B), while RVEF with a cut-off of 40% (Sens: 88%, Spec: 33%) was unable to predict this response (Figure C.). <h3>Conclusion</h3> In CAD patients undergoing general anaesthesia, hyperoxia has heterogenous effects on the RV and the potential detrimental effects of hyperoxia were best predicted by RVGLS. Intraoperative strain analysis might be a tool to target oxygen levels based on individual needs.

Recruitment strategies for a post cessation weight management trial: A comparison of strategy cost-effectiveness and sample diversity

BackgroundEffective recruitment of representative and diverse samples in research trials is important to the generalizability of findings and in describing access to behavioral interventions. The current study evaluated the effectiveness of local and national recruitment strategies for a smoking cessation and weight management-focused randomized controlled trial (Fit & Quit). The overall cost-effectiveness of recruitment strategies was also evaluated. MethodsThe study initially recruited participants locally in the Memphis, TN area and later transitioned to national recruitment, necessitated by the transition to remote assessment strategies due to the COVID-19 pandemic. The study evaluated effective recruitment strategies for randomized participants (n = 305) across gender, race, rurality, and recruitment method, as well as the cost-effectiveness of methods used during the recruitment period of this study. ResultsThe most effective recruitment strategies were local postcards, local radio advertisements, word-of-mouth referrals, and national internet advertisements, which resulted in a combined 71.8% (n = 219) of the total randomized sample (n = 305). Radio advertisements were the best method for recruiting Black participants. Electronic recruitment strategies were the most effective method for non-urban participants. Additionally, gender, recruitment method, race, and rurality predicted randomization. Overall, electronic media methods were more cost-effective ($430.97 per participant) compared to traditional media methods ($931.43 per participant); however, traditional media methods resulted in a greater number of recruited and randomized participants. ConclusionResults provide information on effective and cost-effective local and national recruitment methods for recruiting underrepresented groups of participants in behavioral clinical intervention studies.