Enrollment Of Participants Research Articles

Prospective, Phase III Study of the Efficacy, Safety, and Pharmacokinetics of a Human Antithrombin III Concentrate in Congenital Antithrombin Deficiency during Surgery or Childbirth

Introduction: Congenital antithrombin deficiency (CAD) is a rare genetic blood disorder commonly associated with spontaneous thrombotic events (TEs) and thromboembolic events (TEEs) that can occur in connection with surgery and childbirth. Although regular prophylactic antithrombin substitution is not necessary, human plasma-derived antithrombin replacement therapy or recombinant antithrombin replacement therapy can be used for the prevention of TEs/TEEs during and after surgery or childbirth. This study will aim to evaluate the efficacy, safety, and pharmacokinetics (PK) of a high-purity, double virus inactivated, lyophilized human antithrombin III concentrate (Atenativ ®) in these settings.Methods: The ATN-106 study (NCT04918173) is a multicenter, prospective, interventional, single-group, open-label, Phase III study in adult (≥18 and ≤80 years) male and female patients with documented CAD (plasma antithrombin ≤60%), and personal or family history of TEs or TEEs. The study will enrol 34 patients with CAD, including >14 non-pregnant patients for the PK phase and ~20 patients who are either a) non-pregnant and scheduled to undergo an elective surgical procedure known to be associated with a high risk for occurrence of TEs or TEEs, or b) pregnant and scheduled for caesarean section or delivery.For PK analysis, patients will receive a single 60 IU/kg intravenous (IV) infusion of antithrombin concentrate. For efficacy and safety analyses, a single IV dose to target an antithrombin level of 120% of normal will be administered to patients prior to surgery/delivery followed by maintenance doses administered every 24 hours for ~2-7 (surgical patients) or ~5 (delivery patients) days to target an antithrombin level of 80-120% of normal. A schematic representation of the ATN-106 study design is presented in Figure 1.The primary outcome measure will be the incidence of the composite of TEs and TEEs; secondary outcome measures will include single-dose PK (area under the curve [AUC norm(0-∞)], maximum plasma concentration [C max], half-life [T 1/2], mean residence time [MRT], clearance [CL], incremental in vivo recovery [IVR], volume of distribution at steady state [V ss]) and coagulation (activated partial thromboplastin time [aPTT], prothrombin time [PT], international normalised ratio [INR], fibrinogen level) parameters, as well as safety and tolerability (number of adverse events [AEs]).Results: Enrollment of participants in the ATN-106 study is estimated to start in Q3 2021 and end in Q3 2024.Conclusions: The results from this pivotal registration study are expected to confirm and strengthen the available evidence indicating that human plasma-derived antithrombin concentrate is effective in preventing thrombotic and thromboembolic events in patients with CAD in surgery and delivery settings and has a favorable safety profile. [Display omitted] DisclosuresSchwartz: Octapharma: Current Employment. Solomon: Octapharma: Current Employment. Knaub: Octapharma: Current Employment. Kessler: Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Early Findings on the Use of Motion Capture during Simulated Sports Activities to Better Understand Hemophilic Arthropathy

Many persons with hemophilia (PwH) have joint bleeding despite prophylaxis. We hypothesize that movement biomechanics play a significant and largely unexplored role in joint bleeding, which could be exploited to develop personalized rehabilitation programs. We have designed a clinical study to test this hypothesis. Here we show data from the first 3 enrollees as case studies of what could potentially be learned.Data were collected from 3 participants with hemophilia A, ages 10-30 years, on prophylaxis with emicizumab, with at least 1 joint bleed in the lower extremity in the past year, using motion capture techniques with force plates and reflective markers collected through a Vicon system. Motion lab activities were designed to simulate sports activities and included walking (barefoot and shod), squatting (double and single leg), hopping on one foot, and jumping from a 30-cm box. Two patients (B and C) routinely take additional factor VIII prophylaxis prior to physical activity and did so before coming to the motion lab. Hemophilia Joint Health Score (HJHS) was obtained by an experienced physical therapist prior to motion lab collection to gauge degree of hemophilic arthropathy by physical exam. A subset of participants and activities are shown graphically.Participant A (not shown) had a higher HJHS in the right knee than left (3 vs 0) and had HJHS of 4 in bilateral ankles, with most recent bleed in the right ankle 8 months prior; primary physical activity was walking. This participant showed subtle differences between the right and left in all activities, including less weight on the right leg during double leg squat, and right single leg hop lower than the left.Participant B had a higher HJHS in the right knee than the left (3 vs 0) and in the right ankle than the left (7 vs 6), and he had had multiple episodes of knee pain but no change in HJHS since 2 years prior. Knee MRIs performed outside of the study were consistent with tendinosis of bilateral quadriceps rather than bleeding. Primary sports were basketball, hiking, biking, and skiing. Participant B had subtle differences between the right and left side that seemed to protect the right, including mildly decreased right knee flexion with weight acceptance during walking (more pronounced when wearing shoes), lower power generation by the right ankle than the left in walking, and lower peak ground reaction force (GRF) on the right than left in forward hopping. Some motions seemed to protect the left side more, with less power generation and absorption by the ankle (double and single leg squats) and hip (single leg squat only), right single leg squat somewhat deeper than the left, and slower time to step onto the left foot than the right.Participant C had a higher HJHS in the right knee than left (2 vs 1) and in the right ankle than left (5 vs 3) but had had worsening HJHS in bilateral ankles compared to his previous scores, with bleeds in both knees in the past year. Primary physical activities were baseball (pitching), basketball, biking, skiing, and golf. He had recently been diagnosed with Osgood Schlatter (patellar tendon/tibial tuberosity inflammation) of the left knee, which had been causing pain for several months, but no bleeding in that knee. Movement analysis reflected left knee pain, including very little flexion with weight acceptance when walking; very little power absorption or generation from the knee in walking, hopping, and squatting; shallower squats and lower hops on the left; and lower ground reaction force on the left than the right with walking. Perhaps related to the left knee protection, both ankles were consistently more plantarflexed in walking, and there was increased power generation in the right ankle compared to the left.These findings suggest the presence of subtle asymmetry related to hemophilic arthropathy and previous bleeding, which were more pronounced in more strenuous activities than with walking. The results of participant C could suggest that pain, even if unrelated to hemophilia, could cause compensatory movement mechanisms that could lead to increased bleeding risk in other lower extremity joints.Ongoing analysis will include tracking of bleeding over 1 year following motion analysis, enrollment of additional participants, comparison with controls, and performing detailed statistical analysis to determine which movement parameters correlate best with HJHS and lower extremity bleeding risk. [Display omitted] DisclosuresWarren: Novo Nordisk: Consultancy; Hema Biologics: Consultancy; Bayer: Research Funding; CSL Behring: Research Funding; Genentech: Research Funding. Funk: Biomarin: Consultancy; Sanofi Genzyme: Speakers Bureau; Toronto Sick Kids Hospital: Patents & Royalties: Hemophilia Joint Health Score Royalties; Partners: Honoraria.

Characterization of Underrepresented Populations in Modern Era Clinical Trials Involving Radiation Therapy

PurposeThe demographic composition of modern radiation therapy (RT) clinical trials is incompletely studied. Understanding and minimizing disparities in clinical trials is critical to ensure health equity and the generalizability of research findings. Methods and MaterialsClinicaltrials.gov was searched to identify RT clinical trials that occurred from 1996 to 2019. A total of 1242 trials were reviewed for patient characteristics. The demographic composition of the studies was summarized by the frequency and percentage of patients by race, gender, and ethnicity. The racial composition of the study population was compared with the 2018 US Census using a 1-sample χ2 test. Subgroup racial composition was compared using χ2 tests of independence. Analyses used a complete case approach. ResultsA total of 122 trials met the inclusion criteria, and 121 of these (99.1%) reported race. Trial subgroups included 63 trials in the United States (51.6%), 9 proton therapy trials (7.4%), 34 RT toxicity mitigation or prevention trials (27.9%), 24 trials for female cancer (19.7%), and 17 trials for male cancer (13.9%). US clinical trials overall, US RT toxicity mitigation or prevention trials, US trials for female cancer, and US trials for male cancer had significantly different racial compositions compared with the 2018 US Census data (P < .001 for all). Compared with all clinical trials, those for proton therapy had the largest magnitude of significantly lower enrollment of participants who identified their race as Black, Asian, or other (P < .001). ConclusionsThis study characterized the racial composition of prospective RT clinical trials in a modern cohort. The racial population represented across multiple categories in the United States differed significantly from US census data and was most pronounced in trials evaluating proton therapy. This is a benchmark study for future efforts to characterize and balance the participation of underrepresented populations in RT clinical trials.

Increasing Black, Indigenous and People of Color participation in clinical trials through community engagement and recruitment goal establishment.

Longstanding social and economic inequities elevate health risks and vulnerabilities for Black, Indigenous and People of Color (BIPOC) communities. Engagement of BIPOC communities in infectious disease research is a critical component in efforts to increase vaccine confidence, acceptability, and uptake of future approved products. Recent data highlight the relative absence of BIPOC communities in vaccine clinical trials. Intentional and effective community engagement methods are needed to improve BIPOC inclusion. We describe the methods utilized for the successful enrollment of BIPOC participants in the U.S. Government (USG)-funded COVID-19 Prevention Network (CoVPN)-sponsored vaccine efficacy trials and analyze the demographic and enrollment data across the efficacy trials to inform future efforts to ensure inclusive participation. Across the four USG-funded COVID-19 vaccine clinical trials for which data are available, 47% of participants enrolled at CoVPN sites in the US were BIPOC. White enrollment outpaced enrollment of BIPOC participants throughout the accrual period, requiring the implementation of strategies to increase diverse and inclusive enrollment. Trials opening later benefitted considerably from strengthened community engagement efforts, and greater and more diverse volunteer registry records. Despite robust fiscal resources and a longstanding collaborative and collective effort, enrollment of White persons outpaced that of BIPOC communities. With appropriate resources, commitment and community engagement expertise, the equitable enrollment of BIPOC individuals can be achieved. To ensure this goal, intentional efforts are needed, including an emphasis on diversity of enrollment in clinical trials, establishment of enrollment goals, ongoing robust community engagement, conducting population-specific trials, and research to inform best practices.

Comparison of analgesic effects of Gabapentin and Paracetamol post-operatively in patients with hand injury.

To compare the analgesic effects of gabapentin and paracetamol post-operatively in patients with hand injury. The double-blind, randomised control trial was conducted at the Department of Plastic Surgery, Dow University of Health Sciences, Karachi, from March to August 2019, and comprised subjects aged 18-60 years with hand injury who were randomly divided into group I which received gabapentin 600mg and group II which received paracetamol 1000 mg through anonymous packaging. Pain intensity was assessed using the visual analogue scale along with a self-designed questionnaire which was filled twice post-operatively; first at the time of drug intake once orally allowed; and thereafter six hours later. Data was analysed using SPSS 22. Of the 50 subjects, there were 25(50%) in each of the two groups. Overall, there were 41(82%) males and 9(18%) females. The mean age of the total sample was 28.64±6.72 years. The most frequent side-effect reported in both groups was nausea; 11(44%) in group I and 9(36%) in group II. The least reported side-effect in group I was double vision 1(4%) which was not reported at all in group II and the least reported side-effect was dry mouth 1(4%). The analgesic effect between the groups were not significantly different (p>0.05). Both gabapentin and paracetamol were found to be effective in pain management, but the latter had slightly better pain control with relatively less side-effects. ClinicalTrials.gov Identifier: NCT04068506.

Recruitment of Black Adults into Cardiovascular Disease Trials.

BackgroundAlthough disproportionately affected by cardiovascular disease, Black adults remain underrepresented in clinical trials. The National Institutes of Health recommends that studies define goals for recruitment of underrepresented populations. However, the extent to which cardiovascular trials incorporate evidence‐based recruitment strategies in their protocols is understudied.Methods and ResultsWe systematically reviewed National Institutes of Health‐funded cardiovascular clinical trials registered in ClinicalTrials.gov between 2000 and 2019. Based on publicly available or requested protocols, we focused on enrollment of Black adults as well as the following recruitment strategies: community‐based, electronic medical record‐based, and provider‐based recruitment. A total of 100 clinical trials focused on cardiovascular disease were included in our analysis, of which 62% had published protocols, and 46% of trials had enrolled populations that were <25% Black. In our analysis of available trial protocols, 21% of trials defined a recruitment target for underrepresented groups; however, only one study reported achieving its enrollment goal. While 13% of trial protocols referenced community‐based recruitment strategies, 5% explicitly mentioned involving community members in the trial design process. Defining recruitment targets was associated with higher enrollment of Black participants.ConclusionsBlack adults are underrepresented in National Institutes of Health‐funded cardiovascular trials, and the majority of these trials did not specify a Black enrollment target, did not meet targets, and largely did not report specific plans to enroll Black adults in their studies. Future interventions should target trial design and planning phases before study initiation to address these enrollment disparities.

Disparities in the enrollment of racial and ethnic minorities in clinical trials of poly ADP ribose polymerase inhibitors for women's cancers

<h3>Objectives:</h3> Disparities persist in the enrollment of diverse racial and ethnic groups in clinical trials for ovarian and breast cancers. We sought to analyze the enrollment of participants by race/ethnicity in phase II and III clinical trials involving poly ADP ribose polymerase (PARP) inhibitors for ovarian and breast cancers and compare these to the racial/ethnic prevalence of ovarian and breast cancer in the United States. <h3>Methods:</h3> This study was designed as a retrospective review of clinical trials registered with Clinicaltrials.gov. Studies included evaluated PARP inhibitors for the treatment of ovarian, fallopian tube, primary peritoneal, and breast cancers. Enrollment rates for clinical trials were stratified by race/ethnicity and type of cancer. Enrollment fractions (EF) were calculated using prevalence data from the Surveillance, Epidemiology, and End Results (SEER) Database. Odds ratios (OR) and 95% Confidence Intervals (CI) were calculated to compare minority enrollment rates to Non-Hispanic (NH) White enrollment rates. <h3>Results:</h3> A 48 trials were identified, 17 of which met inclusion criteria (12 ovarian, 2 breast and 3 breast and ovarian). For ovarian cancer trials, enrollment fractions were NH-White 1.5%, NH-Black 0.3%, Hispanic 0.5%, and Asian/Pacific Islander the largest at 2.4%. For breast cancer trials, the EF for NH-White participants was 0.005%, for NH-Black patients was 0.008%, for Hispanic patients was 0.003%, and for Asian/Pacific Islander patients, still the highest at 0.009%. Patients identified as NH-Black and Hispanic were significantly underrepresented compared to those identified as NH-White in clinical trials for ovarian cancer (OR 0.23, 95% CI [0.18-0.29] and OR 0.3, 95% CI [0.25-0.38] respectively, <i>p</i>-value of < 0.0001). In breast cancer trials, both NH-Black and Asian/Pacific Islander groups were significantly overrepresented compared to the NH-White (OR 1.54, 95% CI [1.02, 2.33] p=0.042, and OR 1.81, 95% CI [1.01, 3.26] p=0.047 respectively). EF comparisons for ovarian and breast cancer are noted in Table 1. <h3>Conclusions:</h3> NH-Black and Hispanic participants are significantly underrepresented in clinical trials evaluating PARP inhibitors for ovarian cancer compared to NH-White cohorts. Phase II and III trials assessing PARP inhibitors for ovarian and breast cancer do not accurately represent the populations diagnosed with these malignancies. Enrollment strategies are needed to increase diversity in PARP inhibitor clinical trials for women's cancers.

Evaluating Vaccine Efficacy Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Although interim results from several large, placebo-controlled, phase 3 trials demonstrated high vaccine efficacy (VE) against symptomatic coronavirus disease 2019 (COVID-19), it is unknown how effective the vaccines are in preventing people from becoming asymptomatically infected and potentially spreading the virus unwittingly. It is more difficult to evaluate VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than against symptomatic COVID-19 because infection is not observed directly but rather is known to occur between 2 antibody or reverse-transcription polymerase chain reaction (RT-PCR) tests. Additional challenges arise as community transmission changes over time and as participants are vaccinated on different dates because of staggered enrollment of participants or crossover of placebo recipients to the vaccine arm before the end of the study. Here, we provide valid and efficient statistical methods for estimating potentially waning VE against SARS-CoV-2 infection with blood or nasal samples under time-varying community transmission, staggered enrollment, and blinded or unblinded crossover. We demonstrate the usefulness of the proposed methods through numerical studies that mimic the BNT162b2 phase 3 trial and the Prevent COVID U study. In addition, we assess how crossover and the frequency of diagnostic tests affect the precision of VE estimates.

Feasibility and Acceptability of a Smoking Cessation Program for Individuals Released From an Urban, Pretrial Jail

Tobacco use prevalence among individuals involved in the criminal-legal system is 125% higher than that of the general population and leads to high levels of smoking-related morbidity and mortality. To examine the acceptability, feasibility, and preliminary clinical outcomes of a smoking cessation intervention for individuals who are incarcerated. This pilot randomized clinical trial was conducted from January 2019 to May 2020. Participants were recruited in a pretrial county jail in a large Midwestern US city and were followed up after release. Participants were incarcerated, smoked daily before incarceration, desired to stay quit or reduce cigarette smoking upon release, and expected to be released to the community within 90 days of enrollment. Data analysis was performed from June to October 2020. Participants randomized to the counseling plus nicotine replacement therapy (NRT) group received 1 hour of smoking cessation counseling in jail, a supply of nicotine lozenges upon release, and up to 4 telephone counseling sessions after release. Those randomized to brief health education (BHE) received 30 minutes of general health education in jail. The primary clinical outcome was biologically verified 7-day point prevalence abstinence (PPA) at 3 weeks after release. Secondary clinical outcomes included 7-day PPA at 12 weeks, changes in number of cigarettes per day, and time to smoking lapse and relapse. A total of 46 participants (42 men [91%]; mean [SD] age, 38.2 [9.1] years) were enrolled and remained eligible at release; 23 were randomized to the counseling plus NRT group and 23 were randomized to the BHE group. Recruitment, enrollment, and retention of participants was feasible and acceptable. There were no significant differences in smoking abstinence between groups as determined by 7-day PPA at 3 weeks (adjusted 7-day PPA, 11.9% for counseling plus NRT vs 10.6% for BHE; odds ratio, 1.13; 95% CI, 0.14-9.07) and at 12 weeks (adjusted 7-day PPA, 11.1% for counseling plus NRT vs 14.3% for BHE; odds ratio, 0.75; 95% CI, 0.09-6.11). Cigarettes per day for the counseling plus NRT group decreased more compared with the BHE group at both 3 weeks (difference [SE], -4.58 [1.58] cigarettes per day; 95% CI, -7.67 to -1.48 cigarettes per day; P = .007) and 12 weeks (difference [SE], -3.26 [1.58] cigarettes per day; 95% CI, -5.20 to -0.20 cigarettes per day; P = .04) after release. Initiation of counseling plus NRT during incarceration and continuing after release is feasible and acceptable to participants and may be associated with reduced cigarette use after release. However, additional supports are needed to increase engagement in telephone counseling after release. A larger clinical trial is warranted to determine the effectiveness of counseling plus NRT. ClinicalTrials.gov Identifier: NCT03799315.

Increased Utilization of Virtual Visits and Electronic Approaches in Clinical Research During the COVID-19 Pandemic and Thereafter

ObjectivesTo assess the impact of the COVID-19 pandemic on clinical research and the use of electronic approaches to mitigate this impact. MethodsWe compared the utilization of electronic consenting, remote visits, and remote monitoring by study monitors in all research studies conducted at Mayo Clinic sites (Arizona, Florida, and Minnesota) before and during the COVID-19 pandemic (ie, between May 1, 2019 and December 31, 2020). Participants are consented through a participant-tracking system linked to the electronic health record. ResultsBetween May 2019, and December 2020, there were 130,800 new consents across every modality (electronic and paper) to participate in a non-trial (107,176 [82%]) or a clinical trial (23,624 [18%]). New consents declined from 5741 in February 2020 to 913 in April 2020 but increased to 11,864 in November 2020. The mean (standard deviation [SD]) proportion of electronic consent increased from 22 (2%) before to 45 (20%) during the pandemic (P=.001). Mean (SD) remote electronic consenting increased from 0.3 (0.5%) to 29 (21%) (P<.001). The mean (SD) number of patients with virtual visits increased from 3.5 (2.4%) to 172 (135%) (P=.003) per month between pre-COVID (July 2019 to February 2020) and post-COVID (March to December 2020) periods. Virtual visits used telemedicine (68%) or video (32%). Requests for remote monitor access to complete visits increased from 44 (17%) per month between May 2019 and February 2020 to 111 (74%) per month between March and December 2020 (P=.10). ConclusionAfter a sharp early decline, the enrollment of new participants and ongoing study visits recovered during the COVID-19 pandemic. This recovery was accompanied by the increased use of electronic tools.

Impact of coronavirus disease-19 pandemic on pediatric vaccine clinical trials

Introduction: The coronavirus disease (COVID)-19 pandemic has affected nearly every facet of life, including clinical research, and has had an adverse and extensive impact on clinical trials including pediatric vaccine trials. Across the globe, countries implemented a variety of restrictions to people’s everyday lives, which have substantially impacted the ability to conduct pediatric vaccine trials. Objectives: The objectives of the study were to assess the impact of the COVID-19 pandemic on enrollment and follow-up of clinical trial participants in pediatric vaccine clinical trials and simultaneously to explore various strategies used for overcoming these challenges during the COVID-19 pandemic period. Materials and Methods: Data of 10 pediatric vaccine clinical trials were obtained from the clinical trial records of the Clinical Research Unit. The number of subjects enrolled, number of study dropouts, protocol deviations, and reasons for participant dropout/deviations were recorded from these pediatric vaccine clinical trials carried out before and during the COVID-19 pandemic period from March to December 2020. These metrics were then compared with their counterparts recorded during our study to statistically assess the impact of the COVID-19 pandemic. Various factors which have affected the recruitment and follow-up in pediatric vaccine clinical trials and various strategies used to curtail subject dropout and protocol deviations during COVID-19 pandemic were studied in detail. Results: The primary and most visible impact of the COVID-19 pandemic was that protocol deviations and study dropouts were significantly higher for the trials conducted during COVID-19 pandemic period. The difference between proportion of protocol deviations and study dropouts in the pediatric vaccine clinical trials conducted during pandemic and trials conducted before pandemic was statistically significant (&lt;0.05). The recruitment for ongoing trials was also adversely affected. Conclusion: At our site, the COVID-19 pandemic has affected the conduct and recruitment of pediatric vaccine trials markedly in an adverse manner. The protocol deviations and study dropout were significantly higher during the COVID-19 pandemic period. To counter these effects and still have the trials retain their effectiveness, we found that it is essential to implement measures and strategies for maintaining compliance and safe conduct of clinical trials. Adoption of telemedicine may offer promise in terms of a way forward for conducting clinical trials.

Preliminary Results from Accelerate, an International, Web-Based, Natural History Registry of Castleman Disease

Introduction: Castleman disease (CD) describes a heterogeneous group of disorders that share characteristic histopathological lymph node features. Unicentric CD (UCD) involves localized lymphadenopathy whereas multicentric CD (MCD) involves generalized lymphadenopathy, cytokine-driven systemic inflammatory symptoms, and life-threatening multiple organ system dysfunction. Uncontrolled Human Herpesvirus 8 (HHV-8) infection causes approximately half of MCD cases (HHV-8-associated MCD). The etiology of HHV-8-negative MCD is unknown or idiopathic (iMCD). Currently, there is a lack of clinical and laboratory data describing the 3 subtypes of CD and their natural histories. Further, a systematic analysis of treatments for each subtype has not been performed. Acknowledging these gaps, the field prioritized the development of a natural history study of CD, ACCELERATE, which began enrollment in 2016. The primary objective of ACCELERATE is to collect real world data on the natural history and treatment of patients with CD.Methods: ACCELERATE employs a unique two-armed approach to enroll individuals, who have had a lymph node pathology report suggesting “Castleman disease.” The “physician-directed arm” (PDA) consists of 10 study sites located in 6 European countries, a traditional paper-based patient consent, and physician data entry via a web-based portal. In contrast, the “patient-powered arm” (PPA) involves a web-based platform through which participants located anywhere outside of Europe can enroll directly at www.CDCN.org/ACCELERATE. Once enrolled in the PPA, medical records, including pathology images, are obtained and data is extracted into the web-based portal by the ACCELERATE Registry Team (ART). Analyses of demographic, select clinical and laboratory, and treatment data were performed in cases with complete extracted records. A Certification & Access Subcommittee will review all cases to grade the quality of data that exist in favor of a CD diagnosis. iMCD diagnosis is based on recently-published consensus criteria.Results: Since launching in August 2016, 51 subjects have consented, satisfied inclusion criteria, and completed all enrollment forms. The ART has completed extraction of medical records into the database for 15 patients, including 9 iMCD participants and 6 UCD participants. There were 4 females with iMCD and 3 with UCD. The median age at diagnosis was 31 (range: 14-58) for iMCD and 38.5 (range: 10-52) for UCD. Six iMCD patients demonstrated hyaline vascular or hypervascular histopathological features, 2 had mixed features, and 1 had plasmacytic features. All 6 UCD patients demonstrated hyaline vascular features. A greater number of clinical and laboratory abnormalities were observed in iMCD patients compared to UCD patients (Table 1). Four of the UCD patients received surgical excision as the sole therapy, and 2 were treated with surgical excision plus medical therapy with a corticosteroid or rituximab. Twenty-two different medications, including 4 different corticosteroids, were used to treat iMCD patients. Medications used simultaneously were classified as regimens. Twenty unique regimens were used, 7 of which included the anti-IL-6 monoclonal antibody, siltuximab, which is the only FDA-approved iMCD treatment. On average, each iMCD patient was treated with approximately 4.3 different regimens after diagnosis (mean time: 3.3 years). Regimens administered more than once to the iMCD cohort included: corticosteroid (CS) monotherapy (n=5), siltuximab+CS (n=5), rituximab monotherapy (n=4), tocilizumab+CS (n=4), siltuximab monotherapy (n=3), rituximab+CS (n=3), and rituximab+cyclophosphamide+CS (n=2).Conclusions: The ACCELERATE Registry is a powerful tool for gathering international clinical and laboratory data for CD. It will allow investigators to describe the natural history of CD and provide a database for testing new hypotheses. Information gathered from the registry may lead to refinements in the diagnostic criteria and improved insights into disease management. Based on this preliminary analysis, it is evident that CD is a heterogeneous disease that is treated with a variety of therapeutic strategies. As sample size increases, we will gain critical insights into treatment effectiveness. We are actively seeking increased enrollment of participants around the world at www.CDCN.org/ACCELERATE. [Display omitted] DisclosuresFajgenbaum:Janssen Pharmaceuticals: Research Funding. Liu:Evercore ISI: Employment. Lukac:PAREXEL International Czech Republic s.r.o, on behalf of Janssen Pharmaceuticals: Employment. Guilfoyle:Janssen: Employment, Equity Ownership. Tendler:Janssen Pharmaceuticals: Employment, Equity Ownership. Uldrick:National Institutes of Health: Patents & Royalties: immunomodulatory compound for KSHV malignancies (Inst); Merck: Research Funding; Celgene: Research Funding; Roche: Research Funding.

Accrual of Black participants to cancer clinical trials following a five-year prospective initiative of community outreach and engagement.

100 Background: Accrual of Black participants to cancer clinical trials remains a major challenge across the country. Here, we report the outcomes of a five-year initiative of community outreach and engagement to improve enrollment of adult Black participants to clinical trials at the Abramson Cancer Center (ACC) at the University of Pennsylvania. Methods: Primary metrics were the percentage of Black patients among all cancer cases in our catchment area, the percentage of adult Black patients cared for at the ACC, and the percentage of adult Black participants enrolled on the three types of NCI-defined clinical trials. Results: In 2014, at baseline, Black residents comprised 19% of the population and 16.5% of cancer cases in our catchment area surrounding Philadelphia, but only 11.1% of ACC patients were Black. The percentages of Black participants accrued onto treatment, non-therapeutic interventional, and non-interventional trials were 12.2%, 8.3%, and 13.0%, respectively. We then established a center-wide program with community guidance to address these gaps. Key elements of the program included: 1) culturally tailored marketing strategies for cancer clinical trials; 2) plans for each protocol to facilitate Black participant enrollment; 3) new partnerships with faith-based organizations serving Black communities to conduct educational events about clinical trials; 4) pilot programs with Lyft and Ride Health to address transportation barriers; 5) patient education by nurse navigators regarding cancer and clinical trials; and 6) an improved informed consent process. These efforts reached more than 10,000 individuals in venues including churches, neighborhoods, community parks and centers, and health centers with formats ranging from educational forums to wellness fairs. Reassessing metrics in 2018, we found that the percentage of Black patients seen at ACC had increased to 16.2%, matching the percentage of Black cancer patients among all cancer cases in our catchment area (16.5%). Total cancer clinical trial accrual had increased from 9,308 participants in 2014 to 13,170 in 2018 (41.5% increase). The percentages of Black participants accrued onto treatment, non-therapeutic interventional, and non-interventional trials were 23.9%, 33.1%, and 22.5%, respectively – a 1.7- to 4.0-fold increase in five years and higher than the percentage of Black patients seen at the ACC. Conclusions: Our multifaceted, community-based engagement initiative to encourage clinical trial enrollment was associated with improved accrual of Black participants to cancer clinical trials. These findings also suggest that gaps in access to cancer centers are a key factor driving access to clinical trials. Medicaid expansion occurred concurrently in all states in our catchment area and its impact on accrual merits further research.

Comparison of Challenges and Problems Encountered in the Practice of Exclusive Breast Feeding by Primiparous and Multiparous Women in Rural Areas of Sindh, Pakistan: A Cross-Sectional Study.

Introduction: The UNICEF (United Nations International Children Education Fund) and WHO (World Health Organization) recommend exclusive breastfeeding (EBF) for the first six months of life. EBF is considered to be an important practice for enhancing infant health and wellbeing. Breastfeeding offers a wide range of psychological and physical health benefits in the long-term and short-term for young children, infants, and mothers. This study aims to compare exclusive breastfeeding practice among primiparous and multiparous mothers including reasons for discontinuing exclusive breastfeeding and problems faced during breastfeeding.Methodology: This cross-sectional study was conducted in rural areas of Sindh, registered with the Maternal Newborn Health Registry (MNHR). The study used a systematic sampling technique for the enrollment of study participants. A survey questionnaire was used to collect data from mothers about the practices of EBF. A total of 397 mothers were interviewed and analyzed.Results: Among Primiparous mothers, 14.1% of mothers initiated breastfeeding within one hour of birth, while 22.4% of multiparous mothers, initiated breastfeeding within one hour of birth. The difference between the two is statistically insignificant (p-value=0.234). A high percentage of multiparous mothers exclusively breastfed their infants for six months (63.5%) as compared to primiparous mothers (51.5%). The most common reason for introducing pre-lacteal feed before six months among primiparous mothers is the lack of adequate milk production to fulfill baby needs; this was the case for 35.4% of mothers. On the other hand, the baby remaining hungry post breastfeeding was the major reason among multiparous mothers (44.0%) for introducing pre-lacteal feed before six months.Conclusion: This study helped in the identification of issues faced by primiparous and multiparous mothers during exclusive breastfeeding. Interventions for promoting EBF need to be tailored as per the need and challenges of the population.

Staff and participant perceptions of optimal recruitment and retention strategies for biomedical cohort studies in the Caribbean.

PurposeTo identify staff and participants perspectives of best practices that facilitate achieving enrollment and retention targets in biomedical cohort studies in Caribbean populations.MethodsEight focus group discussions (FGDs) were held with research stakeholders including research (i) nurses/study supervisors, (ii) field staff/data collectors, and (iii) rural and urban participants of the Third Jamaica Health and Lifestyle Survey (a national NCD risk factor survey with biospecimen collection) to capture qualitative data on experiences with recruitment, training, retention challenges and potential solutions or strategies for strengthening future efforts.ResultsOur findings indicate that trained, experienced study staff with good interpersonal communication skills enhanced the proficiency of field operations and attracted study participants. Targeted community and stakeholder engagement alongside strong support from the coordinating center increased the reach and efficiency of the data collectors. Timely participant feedback, gender-appropriate approaches, and socioeconomic balance enhanced equitable enrollment and retention of participants of cohort studies particularly the hard to reach groups.ConclusionWell-functioning research teams using traditional and social media promotion, applying gender-appropriate and personalized approaches together with strategies for reaching the less accessible socioeconomic groups, are effective for recruiting and retaining members of a Caribbean cohort. These strategies may also enhance the recruitment of other Black populations in the Diaspora including the US and Caribbean into biomedical studies including cancer research.

Recruitment and enrollment of participants in an online diabetes self-management intervention in a virtual environment

Effective recruitment of research participants is essential for successful randomized controlled trials and remains one of the most challenging and labor-intensive aspects of conducting research. The purpose of this manuscript is to describe recruitment methods for this two-group, internet-based intervention trial and enrollment status in relation to recruitment methods, accounting for accrual rates and recruitment costs and to discuss our recruitment results and limitations informed by the Clinical Trials Transformation Initiative (CTTI) team's evidence and expert-based recommendations for recruitment. The primary study was a two-group randomized controlled trial designed to evaluate the efficacy of a virtual environment, Diabetes LIVE©, compared to a traditional website format to provide diabetes self-management education and support to adults with type 2 diabetes. Our recruitment experience was labor-intensive, multimodal, and required multiple iterations throughout the study to meet recruitment goals. To allow for more efficient and realistic budgets aligned with funding, researchers should engage stakeholders in recruitment planning and monitor and report personnel time and cost by recruitment methods. To allow for more efficient and effective recruitment into meaningful clinical trials and of interest to participants, researchers should use a participative approach during all study phases, including question development.

Description and Analysis of Characteristics of COVID-19 Clinical Trials Registered in the Clinical Trials Registry-India (CTRI)

Many clinical trials are ongoing in India to evaluate the efficacy and safety of various interventions in COVID-19. It is mandatory that the clinical trials be registered in the Clinical Trials Registry-India (CTRI) before enrollment of study participants. The present study was carried out with the objective of collecting, compiling and analyzing various types of trial data such as study design, interventions, outcomes and study sites. The clinical trial data were collected from the CTRI web portal using the key word “COVID-19” on 14 July 2020. The CTRI data output of every study registered till 14 July 2020 was stored as PDF document and the data were transcribed into a validated excel sheet based on the pre-defined methods and categories and analyzed. A total of 293 clinical studies have been registered in CTRI as on 14 July 2020. Among them, 188 (64.16%) are interventional and 105 (35.83%) are observational studies. The interventions being evaluated are modern medications including drugs and biologicals, AYUSH formulations, Nutraceuticals, Yoga and Naturopathy. Most of the interventions are already in clinical use for non-COVID indications and undergoing repurposing evaluations for COVID-19 in the clinical studies. Trials with AYUSH formulations constitute more than half of the interventional studies (51.06%) while modern medications in 31.09% of the studies. 119 trials (63.3%) of the interventional studies are randomized studies. Large numbers of trials are conducted in the states where the incidence of COVID-19 is high. 146 interventional studies out of 188 are expected to be completed within 6 months and the outcomes of these studies may provide valid information on the potential treatments in COVID-19.

Registered Trials on Artificial Intelligence Conducted in Emergency Department and Intensive Care Unit: A Cross-Sectional Study on ClinicalTrials.gov.

Objective: Clinical trials contribute to the development of clinical practice. However, little is known about the current status of trials on artificial intelligence (AI) conducted in emergency department and intensive care unit. The objective of the study was to provide a comprehensive analysis of registered trials in such field based on ClinicalTrials.gov.Methods: Registered trials on AI conducted in emergency department and intensive care unit were searched on ClinicalTrials.gov up to 12th January 2021. The characteristics were analyzed using SPSS21.0 software.Results: A total of 146 registered trials were identified, including 61 in emergency department and 85 in intensive care unit. They were registered from 2004 to 2021. Regarding locations, 58 were conducted in Europe, 58 in America, 9 in Asia, 4 in Australia, and 17 did not report locations. The enrollment of participants was from 0 to 18,000,000, with a median of 233. Universities were the primary sponsors, which accounted for 43.15%, followed by hospitals (35.62%), and industries/companies (9.59%). Regarding study designs, 85 trials were interventional trials, while 61 were observational trials. Of the 85 interventional trials, 15.29% were for diagnosis and 38.82% for treatment; of the 84 observational trials, 42 were prospective, 14 were retrospective, 2 were cross-sectional, 2 did not report clear information and 1 was unknown. Regarding the trials' results, 69 trials had been completed, while only 10 had available results on ClinicalTrials.gov.Conclusions: Our study suggest that more AI trials are needed in emergency department and intensive care unit and sponsors are encouraged to report the results.

Pragmatic randomized trial evaluating pre-operative aqueous antiseptic skin solution in open fractures (Aqueous-PREP): the feasibility of a cluster randomized crossover study

BackgroundPreoperative antiseptic skin solutions are used prior to most surgical procedures; however, there is no definitive research comparing infection-related outcomes following use of the various solutions available to orthopedic trauma surgeons. The objective of this pilot study was to test the feasibility of a cluster randomized crossover trial that assesses the comparative effectiveness of a 10% povidone-iodine solution versus a 4% chlorhexidine gluconate solution for the management of open fractures.MethodsTwo orthopedic trauma centers participated in this pilot study. Each of these clinical sites was randomized to a starting solution (povidone-iodine solution or chlorhexidine gluconate) then subsequently crossed over to the other treatment after 2 months. During the 4-month enrollment phase, we assessed compliance, enrollment rates, participant follow-up, and accurate documentation of the primary clinical outcome. Feasibility outcomes included (1) the implementation of the interventions during a run-in period; (2) enrollment of participants during two 2-month enrollment phases; (3) application of the trial interventions as per the cluster randomization crossover scheme; (4) participant follow-up; and (5) accurate documentation of the primary outcome (surgical site infection). Feasibility outcomes were summarized using descriptive statistics reported as means (standard deviation) or medians (first quartile, third quartile) for continuous variables depending on their distribution and counts (percentage) for categorical variables. Corresponding 95% confidence intervals (CIs) were also reported.ResultsAll five of the criteria for feasibility were met. During the run-in phase, all 18 of the eligible patients identified at the two clinical sites received the correct cluster-assigned treatment. A total of 135 patients were enrolled across both sites during the 4-month recruitment phase, which equates to 92% (95% CI 85.9 to 96.4%) of eligible patients being enrolled. Compliance with the assigned treatment in the pilot study was 98% (95% CI 93.5 to 99.8%). Ninety-eight percent (95% CI 93.5 to 99.8%) of participants completed the 90-day post-surgery follow-up and the primary outcome (SSI) was accurately documented for 100% (95% CI 96.6 to 100.0%) of the participants.ConclusionsThese results confirm the feasibility of a definitive study comparing antiseptic solutions using a cluster randomized crossover trial design. Building upon the infrastructure established during the pilot phase, a definitive study has been successfully initiated.Trial registrationClincialTrials.gov, number NCT03385304. Registered December 28, 2017.

Assessment of the Inclusion of Racial/Ethnic Minority, Female, and Older Individuals in Vaccine Clinical Trials

Medical research has not equitably included members of racial/ethnic minority groups or female and older individuals. There are limited data on participant demographic characteristics in vaccine trials despite the importance of these data to current trials aimed at preventing coronavirus disease 2019. To investigate whether racial/ethnic minority groups and female and older adults are underrepresented among participants in vaccine clinical trials. This cross-sectional study examined data from completed US-based vaccine trials registered on ClinicalTrials.gov from July 1, 2011, through June 30, 2020. The terms vaccine, vaccination, immunization, and inoculation were used to identify trials. Only those addressing vaccine immunogenicity or efficacy of preventative vaccines were included. The numbers and percentages of racial/ethnic minority, female, and older individuals compared with US census data from 2011 and 2018. Secondary outcome measures were inclusion by trial phase and year of completion. A total of 230 US-based trials with 219 555 participants were included in the study. Most trials were randomized (180 [78.3%]), included viral vaccinations (159 [69.1%]), and represented all trial phases. Every trial reported age and sex; 134 (58.3%) reported race and 79 (34.3%) reported ethnicity. Overall, among adult study participants, White individuals were overrepresented (77.9%; 95% CI, 77.4%-78.4%), and Black or African American individuals (10.6%; 95% CI, 10.2%-11.0%) and American Indian or Alaska Native individuals (0.4%; 95% CI, 0.3%-0.5%) were underrepresented compared with US census data; enrollment of Asian individuals was similar (5.7%; 95% CI, 5.5%-6.0%). Enrollment of Hispanic or Latino individuals (11.6%; 95% CI, 11.1%-12.0%) was also low even among the limited number of adult trials reporting ethnicity. Adult trials were composed of more female participants (75 325 [56.0%]), but among those reporting age as a percentage, enrollment of participants who were aged 65 years or older was low (12.1%; 95% CI, 12.0%-12.3%). Black or African American participants (10.1%; 95% CI, 9.7%-10.6%) and Hispanic or Latino participants (22.5%; 95% CI, 21.6%-23.4%) were also underrepresented in pediatric trials. Among trials reporting race/ethnicity, 65 (48.5%) did not include American Indian or Alaska Native participants and 81 (60.4%) did not include Hawaiian or Pacific Islander participants. This cross-sectional study found that among US-based vaccine clinical trials, members of racial/ethnic minority groups and older adults were underrepresented, whereas female adults were overrepresented. These findings suggest that diversity enrollment targets should be included for all vaccine trials targeting epidemiologically important infections.