Clinical Research Trials Research Articles

Quality of Reporting Randomized Controlled Trials Published in Three of the Most Citable Periodontal Journals from 2018 to 2022.

This study aimed to evaluate the reporting quality of randomized clinical trials (RCTs) in periodontology. Three leading periodontology journals, the Journal of Periodontology (JOP), the Journal of Clinical Periodontology (JOCP), and the Journal of Periodontal Research (JOPR), were selected for this investigation. The RCTs were identified by manually searching for human trial articles published in these three journals. Two authors independently conducted the literature search, and a pre-piloted extraction sheet was used to screen the potential RCTs. The CONSORT checklist guidelines were employed to calculate the score value. Intra-examiner reliability was assessed by scoring a random sample of 10% of the papers in a second round conducted by the first examiner three months after the initial data collection. A search of abstracts published over a five-year period yielded 176 articles that reported RCTs, accounting for 11.7% of all articles published in the three journals. The highest number of RCTs was published in 2020, and more than half of the included RCTs (51%) originated from Europe. Many of the analyzed RCTs inadequately reported almost half of the items on the CONSORT checklist. Furthermore, univariate analysis revealed significant associations between certain factors and the overall CONSORT score, such as publication in JOP (p = 0.048), publication year of 2019 (p = 0.041) and 2021 (p = 0.042), first author from North America (p = 0.016), and RCTs with more than six authors (p = 0.042). Clinical trial research in periodontics has made significant progress in the past five years. However, there is room for improvement in adhering to the CONSORT guidelines.

Clinical trial research on furagin-induced anaphylactic shock: assessing mechanisms and preventive strategies

Background. The study investigates the pressing issue of furagin-induced anaphylactic shock, addres-sing the immediate need to understand its mechanisms and create preventive strategies. Anaphylactic shock due to furagin, a widely used antimicrobial drug, has raised serious concerns. The goal is to elucidate the underlying mechanisms and risk factors of furagin-induced anaphylactic shock. Materials and methods. This research delves into this critical subject through a controlled longitudinal study on both humans and induced anaphylaxis in rats. Results. Using an advanced blind controlled longitudinal design, the study evaluates allergic reactions in humans and induced anaphylaxis in rats. It also explores the safety, tolerability, and pharmacokinetics of furagin over five days in adult patients. Moreover, the study assesses the efficacy of antihistamine pre-treatment in reducing allergic reactions. Results reveal a dose-dependent trend in allergic reactions in rats, demonstrating the effectiveness of antihistamine pre-treatment in reducing the severity of allergic symptoms. Patients with previous allergies, especially to medications, exhibited increased susceptibility to furagin-induced anaphylactic symptoms. The study underscores the potential for antihistamine pre-treatment as a preventive strategy and contributes to the understanding of allergic responses. This research informs clinical practice by providing insights into risk factors and preventive measures for furagin-induced hypersensitivity, ultimately enhancing patient safety. Conclusions. The study findings hold promise for personalized interventions and advance our understanding of drug-induced hypersensitivity reactions.

Much work to do about measuring work.

Work ability is a critical economic and well-being indicator in cancer care. Yet, work ability is understudied in clinical trials and observational research and is often undocumented in medical records. Despite agreement on the importance of work from well-being, health insurance, and financial perspectives, standardized approaches for collecting, measuring, and analyzing work outcomes are lacking in the health-care setting. The necessary components for closing the gap in patient and caregiver employment research in health-care settings involve a common set of measures, including those that replace or translate generic measures of mental and physical functioning into work outcomes in observational and clinical trial research, standardized approaches to data collection and documentation, and the use of longitudinal data to understand the consequences of reduced work ability over time. We present a conceptual framework for the inclusion of work ability in outcomes research. We cover constructs for employment and work ability measurement that can be adopted in research, recorded as patient-level data, and used to guide treatment decisions. The inclusion of return to work and hours worked, productivity, and ability to perform in a similar job can support conversations that guide treatment decisions and minimize economic consequences. Our hope is that by considering impact on work ability, improved treatments will be developed, health inequities reduced, and resources directed toward aiding patients and their caregivers in balancing work and health demands.

Embedding stakeholder preferences in setting priorities for health research: Using a discrete choice experiment to develop a multi-criteria tool for evaluating research proposals

We determined weights for a multi-criteria tool for assessing the relative merits of clinical-trial research proposals, and investigated whether the weights vary across relevant stakeholder groups. A cross-sectional, adaptive discrete choice experiment using 1000minds online software was administered to consumers, researchers and funders affiliated with the Australian Clinical Trials Alliance (ACTA). We identified weights for four criteria—Appropriateness, Significance, Relevance, Feasibility—and their levels, representing their relative importance, so that research proposals can be scored between 0% (nil or very low merit) and 100% (very high merit). From 220 complete survey responses, the most important criterion was Appropriateness (adjusted for differences between stakeholder groups, mean weight 28.9%) and the least important was Feasibility (adjusted mean weight 19.5%). Consumers tended to weight Relevance more highly (2.7% points difference) and Feasibility less highly (3.1% points difference) than researchers. The research or grant writing experience of researchers or consumers was not associated with the weights. A multi-criteria tool for evaluating research proposals that reflects stakeholders’ preferences was created. The tool can be used to assess the relative merits of clinical trial research proposals and rank them, to help identify the best proposals for funding.

Abstract A133: Mapping the legal estrangement theory onto known barriers in recruiting diverse participants to clinical trials

Abstract Lack of diversity in clinical trials research has significant health consequences because medications and treatments have varying effects on people based on their demographic, socio-economic, and geographic characteristics. This study uniquely adopts the legal estrangement theory to explain the causes for limited diversity in federally funded clinical trials and offers multi-level strategies that researchers, institutions, the US Department of Health & Human Services (HHS), and Congress can take to increase diversity in clinical trials. Legal estrangement is a theory that represents detachment and alienation from those who created the law. From February to March 2023, researchers reviewed legal and medical literature, news stories, and federal regulations to identify barriers contributing to limited diversity in clinical trials. Using the legal estrangement theory as an overarching guide, three broad themes across the clinical trials literature (i.e., procedural injustice, vicarious marginalization, and structural exclusion) were identified. Procedural injustice refers to when people perceive not being treated with dignity and respect. Vicarious marginalization refers to negative experiences that collectively contribute to feelings of alienation. Structural exclusion refers to the way policies that seem to be race or class-neutral have disproportionate effects on marginalized communities. We found that researcher implicit bias and stereotyping contribute to procedural injustice and vicarious marginalization by discouraging prospective people from joining clinical trials. Structural barriers like inaccessibility to participant-friendly educational materials, ambiguity in grant reporting requirements, lack of strong substantive grant standards, exclusion of LGBTQI+ individuals from grant enrollment reports, and budgetary constraints limit efforts to increase participant diversity in clinical trials. To improve diversity in clinical trials, we recommend improving transparency and communication, building meaningful partnerships with community leaders, requiring cultural competency training for researchers, incorporating automatic and non-autonomic recruitment strategies to circumvent bias, strengthening substantive NIH grant standards, adding gender identities to grant enrollment reports, and requesting greater Congressional funding for clinical trials research. Thus, to improve diversity in federally funded clinical trials, a multi-faceted approach that involves researchers, academic institutions, community members, HHS, and Congress are recommended to reduce procedural injustice, vicarious marginalization, and structural exclusion. Future research is needed to explore the connection between structural barriers to access to clinical trials and disparities in cancer care management and patient outcomes. Citation Format: Cilgy M. Abraham, Denalee M. O'Malley. Mapping the legal estrangement theory onto known barriers in recruiting diverse participants to clinical trials [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A133.

How surgical Trainee Research Collaboratives achieve success: a mixed methods study to develop trainee engagement strategies

ObjectivesThis study aimed to understand the role of surgical Trainee Research Collaboratives (TRCs) in conducting randomised controlled trials and identify strategies to enhance trainee engagement in trials.DesignThis is a mixed...

Abstract A005: The development of a bioethically sensitive education video: Addressing the barriers to African Americans’ and Hispanics’ participation in clinical and genomic research through digital animation

Abstract Introduction: Research advances on effective methods to prevent, diagnose and treat cancer continue to emerge through clinical and genomic research. To ensure the results from these research studies help those who need it most, a diverse population needs to enroll. Despite guidance from authorities, such as the National Institutes of Health, most clinical trial and genomic research participants identify as White. At the participant level, mistrust of research, unawareness of research opportunities and gaps in bioethical knowledge about clinical trials and genomic research remain proven barriers to participating, especially among African Americans (AA) and Hispanics. With the development and access to technology, digital delivery of salient and tailored health education may provide innovative pathways to increase representation of AA and Hispanics in research. Methods: Members from the NCI-funded Partnerships to Advance Cancer Health Equity (PACHE) including experts from the community, healthcare, biomedical research and public health, such as oncologists, cancer geneticists, behavioral scientists and bioethicists collaborated on all phases. A design lab with experience synthesizing complex health messages into brief animations was contracted. The goal was to utilize existing educational resources from the National Cancer Institute and the National Human Genome Research Institute to create a tailored message to address AA's and Hispanics’ beliefs, values and bioethical concerns related to participation in clinical and genomic research. Models of behavior change and communication theories were leveraged to frame key components of the message, which then informed the animated video. Results: Development of the video consisted of six iterative phases: 1) writing sessions; 2) storyboarding; 3) animating; 4) screening/revisions; 5) acceptability testing; 6) finalization. In the last two steps, the video was presented to family members of cancer patients, cancer survivors and community members who provided quantitative and qualitative feedback which informed further edits. The final animated video is approximately five minutes in length and covers several topics including the goal of clinical research, disparities in clinical trials and genomic research participation, genomic research regulations and the purpose of a biobank. Supporting imagery to emphasize specific concepts, such as racial disparities in research, was dispersed throughout the video. A voiceover emphasized key bioethical concepts, including how research participation is safe and voluntary. When possible, characters were designed to resemble the targeted viewing audience. Discussion: Increasing AA and Hispanic participation in clinical and genomic research is imperative to achieving health equity. Tailored messages via short videos may assist in addressing the barriers and facilitators towards research participation and increase intentions to enroll in trials. Future research will evaluate the efficacy of the video through a multi-level framework in real-world settings. Citation Format: Victoria Churchill, Yu-Mei Schoenberger, Vivian L Carter, Windy Dean-Colomb, Roland Matthews, Desiree Rivers, Stephen O Sodeke, Jamirah Chevrin, Brian Rivers. The development of a bioethically sensitive education video: Addressing the barriers to African Americans’ and Hispanics’ participation in clinical and genomic research through digital animation [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A005.

Abstract IA010: American Indian community engagement in culturally respectful cancer interventions

Abstract This 10-minute session begins with a brief overview of strengths within American Indian communities. Cultural perceptions of research are summarized followed by a list of unsuccessful recruitment strategies. Missed opportunities for the inclusion of sufficient numbers of American Indians in national clinical trials will be reviewed. An overview of American Indians’ desire for inclusion in respectful clinical trials research will include an excerpt from Clinical Trials for Native Americans: A Gift for our Children. Healthcare Providers impact on inclusion of underserved populations will be summarized followed by a synopsis based on involvement of competency trained Native Patient Navigators to assist with CT recruitment. Some annoyances practiced by research institutions that negatively impact involvement of American Indian communities will be shared followed by recommendations for increasing engagements. The segment will close with a summary of significant gaps in American Indian cancer research programs. Citation Format: Linda Burhansstipanov. American Indian community engagement in culturally respectful cancer interventions [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr IA010.

Abstract IA030: Ensuring diversity in clinical trials

Abstract It is well known that minorities, particularly Blacks, are underrepresented in cancer prevention, early detection, and treatment trials. However the mortality rates for Blacks are significantly higher than other race/ethnic groups. Research suggests that community involvement is integral to solving public health problems, including involvement in clinical trials-a gold standard. Significant racial/ethnic disparities exist in the accrual of participants for clinical trials. Location and cultural aspects of clinical trials influence recruitment and accrual to clinical trials. Being able to identify and resolve social determinants of health is essential for clinical trial participation. It is increasingly necessary to be aware of defining characteristics, such as location and culture of the populations from which research participants are enrolled. Utilizing embedded community academic sites to adapt clinical trial research in order to increase minority participation in nontherapeutic cancer clinical trials is warranted. Considerable attention has focused on the need to increase underserved racial and ethnic populations in clinical research, especially in light of the cancer health disparities that disproportionately plague these groups. Clinical trial design and implementation are time-consuming and require a multistep process that is complicated by other factors, including eligibility criteria for clinical trials for underserved racial and ethnic populations, recruitment processes, and patients’ misconceptions or lack of information about clinical trials. Georgetown-Lombardi National Capital Area Minority/Underserved NCORP (NCI Community Oncology Research Program) coupled with the Ralph Lauren Center for Cancer Prevention will reveal strategies and approaches instrumental to our success. These efforts resulted in the development of a strong community capacity–building and clinical research cancer recruitment strategy, and improved engagement of the community in clinical research, thus ensuring diversity in clinical trials. Citation Format: Lucile Adams-Campbell. Ensuring diversity in clinical trials [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr IA030.

간호대학생을 위한 팀프로젝트기반 임상시험연구 교육의 효과

Objectives Project-based learning engages students in practical activities related to course contents and has been demonstrated to improve academic performance. Nurses play a particularly important role in promoting clinical trial research as a new professional workforce. An entry-leveled educational course was developed to learn the future professional workforce roles in clinical trial research for nursing students. This study evaluated the effectiveness of a clinical trial research course on the importance and performance of the clinical research coordinators' role, students' recognized achievement, and cooperative self-efficacy.
 Methods Five professional clinical coordinators and two nursing professors developed the four projects on the clinical research processes and roles based on Good Clinical Practice guidelines. Thirteen junior students divided into 4 small groups completed a new project-based clinical research course composed of 8 sessions of clinical field work, discussion, reflection, portfolio, and presentation from September to October 2022. Students responded questionnaires on the importance-performance clinical trial nurses' roles, recognized achievement, and cooperative self-efficacy, and reported the reflective journal on the class. The students' class evaluation data was retrieved and analyzed using importance-performance analysis (IPA) and Wilcoxon signed rank test.
 Results Compared to baseline scores, protocol assessment (z=-2.59, p=.010), protocol planning (z=-1.96, p=.050), and subject recruitment (z=-2.16, p=.031) increased among the 8-section of clinical trial coordinator's roles. Additionally professional role recognition increased after the class (z=-2.25, p=.025). IPA analysis exhibited that nursing students recognized the 8-section clinical trial nurses' roles as more important and more performing. The mean score of nursing students' recognized achievement was high (4.96 points out of 5 points), and cooperative self-efficacy was high (4.37 points out of 5 points) after completing a clinical trial research course.
 Conclusions An entry-leveled educational course on the clinical trial research using project-based learning may expand the possibility of a new professional career for nursing students.

Use of an Advance Chart Preparation Process Improves Overall Care in Pediatric Patients with Sickle Cell Disease

Background: Clinics have mostly used pre-clinic chart reviews to increase efficiency of patient appointments and typically only include the provider the day the patient is seen in the clinic. Additionally, these pre-clinic chart reviews tend to focus only on the biomedical needs of the patients and do not often account for the patients' needs relating to social determinants of health (SDoH). Objective: To improve clinical care consistent with national guidelines and enhance comprehensive care coordination for patients with sickle cell disease (SCD) through an advanced chart preparation process incorporating multi-disciplinary team members (Community Health Worker, Research Coordinators, Nurses, and Medical Providers). Methods: Scheduled chart-prep meetings (CPMs) are held approximately 2 weeks before SCD clinic, and are routinely attended by the SCD team spanning multiple disciplines: community health worker (CHW), research coordinators (RC), nurses, and providers. If additional personnel, such as palliative care, counseling, exercise physiology, dietitian, etc., are needed for CPMs, they are invited in advance to the meeting. In preparation for the CPM, a nurse care coordinator conducts a chart review of each scheduled patient to complete a standardized guided chart prep sheet (Fig. 1). During CPMs, the chart prep sheet is used to discuss each patient to ensure all standard of care guidelines are met along with quality improvement objectives. The guided sheet also addresses personalized medical needs for the individual patient, social needs, school/career plans, transition, subspecialty referrals, and screening for eligibility to participate in open QI and research projects. The CPMs assure optimal completion of the following pre-appointment activities: (1) order placement, (2) acquiring external patient data relevant to the upcoming visit, (3) coordinating other same-day testing/appointments, and (4) accommodating social needs (i.e., transportation). After closing any care gaps, the CPM sheet is incorporated into the clinic appointment flow for brief provider review immediately prior to seeing the patient and to assure completion of all needed assessments. Results: CPMs have improved a variety of patient care metrics, making patient appointments more efficient, comprehensive, and patient-focused, and improving pre and post-appointment coordination of care. The advanced chart preparation process increases efficiency for patients, families, and providers. One example has been the increase of annual TCD completion rates from 50% to 93%, largely accomplished by coordinating TCD and clinic appointments, especially for patients living hours from the clinic. Combining other services and appointments on the same appointment day minimizes transportation needs and maximizes completed referral appointments. Incorporating a patient immunization database into CPMs has improved immunization completion rates significantly, more than doubling the rates for some (Men A from 11% to 93%, Men B from 15% to 83%) (Fig. 2). Overall, the CPMs: 1) maximize quality time with patients, 2) assure discussion of non-medical (interpersonal, school, etc.) issues, 3) encourage patient and family medical education opportunities, 4) emphasize attention to each patient's individual SDoH needs, 5) increase successful care coordination, 6) enhance collaboration among members of the SCD care team, 7) provide ongoing focus on QI initiatives, and 8) facilitate patient enrollment in open clinical studies and research trials. Conclusions: Our multidisciplinary SCD care team found that CPMs result in more efficient, effective, and comprehensive patient- and family-centered care while promoting care collaboration by team members. They promoted adherence to guidelines, as evidenced by significant increases in TCD (up 43%) and immunization rates (average improvement 36%, with biggest improvements 82% and 68%, shown above). In addition, the time put into appointment preparation has allowed us to use more clinic time to develop trusting relationships with the patients and families we serve. Furthermore, this process has facilitated patient participation in QI efforts, new databases, and clinical trials. Such chart prep meetings are easily adaptable to a variety of clinical care teams and health delivery settings.

Engaging Underrepresented Patients in Hematology Clinical Trials through the LLS Impact (Influential Medicine Providing Access to Clinical Trials) Research Grant: A Multi-Institutional Effort

Introduction: Despite governmental and industry-sponsored efforts, clinical trial participation among rural residents and racial and ethnic minorities remains low. The NIH Revitalization Act of 1993 directed the NIH to establish guidelines for inclusion of women and minorities in clinical research. In 2015, the Food and Drug Administration launched an action plan to improve the quality of demographic subgroup data collection, identify barriers to enrollment, employ strategies to increase participation, and promote transparency of related data. However subsequent studies (Green et al. Health Aff. March 2022, Kanapuru et al. Blood Advances. March 2022.) showed no improvement in participation of racial minorities, including Blacks and Hispanics since this plan was enacted. Various complex system- and individual-based factors, including lack of clinical trial availability; lack of diversity in the investigator work force; scant patient and provider awareness of clinical trials; lack of trust in the health care system; and issues with access to care-often driven by financial, geographic, or social constraints (Allison et al. Cureus. Apr 2022.), and stringent eligibility criteria are deemed responsible. The Leukemia & Lymphoma Society (LLS) IMPACT (Influential Medicine Providing Access to Clinical Trials) research grant strives to bridge this unrelenting care gap. Methods: The LLS IMPACT program includes a 5-year research grant which was launched in 2021. The IMPACT grants support the establishment of clinical trial networks involving academic cancer centers (“Hubs”) linked to community clinics and oncology centers (“Spokes”). The program's overall goal is to provide patients access to trials through participation at the community sites. Initially, 3 institutional sites were selected to participate. These institutions had unique and tailored strategies to improve engagement of underrepresented patients, including black, indigenous, people of color, Hispanic, Latina/Latino, and people from rural communities in vastly different climates and local cultures. The IMPACT grant expanded to encompass 4 additional sites given the imminent needs and clamor of the hematology clinical trials community (Figure 1A). The catchment areas and strategies employed at each institution are summarized in the table (Figure 1B). Results: At the start of the grant period, focus was on building clinical research infrastructure and opening non-interventional clinical trials to teach personnel about clinical research and create relationships with patients. Other programs such as webinar series, tumor boards, technological advancements, and educational workshops were also established to enhance engagement among physicians, match patients to clinical trials, and to provide clinical trial education to potential patients. One trial that has seen early success is the CHIVE IMPACT trial, a non-interventional registry and biorepository which has enrolled 24 patients at a rural and underserved site as of July 2023. The purpose of CHIVE is to enroll patients who have clonal hematopoiesis (CH) or are at risk of CH and follow prospectively in efforts to understand risk of progression and potential for early intervention. The Universal Protocol is another biorepository trial which has more than tripled its enrollment number at a community site between 2021 and 2022. Of the 63 patients enrolled in 2022, 66% of them identified as a race other than White. As our core goal is to increase access to interventional trials, we hope to bring industry sponsored phase II and phase III studies to underrepresented areas that serve a broad patient population. Lack of financial resources, lack of transportation and distance to trial sites, and residual distrust of the medical community (e.g., legacy of Tuskegee experiments) are barriers the grantees are focused on overcoming to enroll the intended populations into clinical trials. Conclusion: The innovative strategies employed to expand access to clinical trials for underrepresented population at the various institutions through the LLS's IMPACT research grant can be utilized during clinical trials design and implementation phases to improve generalizability of clinical trials in hematologic malignancies. In the third year of this program, 7 participating sites are engaging impactful strategies (Figure 1B) which will be reported at the end of the grant period.

A Patient-Centric Approach to Sickle Cell Disease Clinical Trials: Integrating Patient Perspectives in the RISE UP Phase 2/3 Trial of Mitapivat for Informed Protocol Design and Associated Patient Community Benefit

Background: Sickle cell disease (SCD) is a genetic blood disorder that affects millions of people worldwide. There are currently limited treatment options and a high unmet need; new therapies - and therefore new trials - are essential. Although there is evidence of growing patient (pt) participation in the drug development processes, there is a lingering suspicion among the community that they are not treated as equal partners and too frequently regarded as mere data sources. Involving pts in planning and execution of clinical trials is essential to improve participation and meet the real needs of the patient community. Mitapivat is a first-in-class, oral, allosteric activator of pyruvate kinase (PK), approved by the United States Food and Drug Administration for the treatment of hemolytic anemia in adults with PK deficiency, by the European Union European Medicines Agency, and the Medicines and Healthcare products Regulatory Agency in Great Britain for the treatment of PK deficiency in adults. The RISE UP phase 2/3 trial (NCT05031780) of mitapivat in pts with SCD was therefore devised to use a new approach to clinical trial design and recruitment that considered pt preferences wherever possible. Objective: Using the RISE UP Phase 2/3 trial, redefine best practices in clinical trial design by asking pts with SCD to describe what matters most to them in a trial setting and by involving them in decision making processes and trial awareness communications. Methods: Nine SCD pts and advocates (five from the US, one from Bahrain, one from France and two from the UK) took part in a series of clinical trial design workshops. Four remote advisory board interviews were held with pts (>16 years of age) and advocates to consult on the RISE UP Phase 2/3 clinical trial design. The insights gained from these consultations were incorporated into the proposed trial protocol design that was subsequently shared with Health Authorities (HAs) for their comment from a regulatory perspective. Once finalized, feedback from HAs was presented to the steering committee to determine whether changes requested by HAs met the needs and barriers-to-uptake expressed during partner consultations. In addition, a group of seven patients were involved in the development of the RISE UP phase 2/3 clinical trial awareness campaign, which sought to educate the community about the RISE UP clinical trial and value of pt participation. Results: Pt contributions to the protocol design included modified inclusion/exclusion criteria and the addition of pain (beyond pain crises) and fatigue as study outcomes. An overview of the community feedback is shown in Table 1. In response to pt input, monthly study visits were implemented for seven months, followed by visits every three months. An open label extension period was also added with visits on the second, fourth, eighth, and twelfth weeks of the extension period, followed by every 3 months up to 1.5 years and every six months thereafter. Taking additional pt input into account, the trial was adjusted to include a recommendation for tailored management of SCD pain crises using a daily diary. Additionally, following patient recommendations, the trial approved reimbursement for study-related travel, lodging, and specific non-study assessments. The RISE UP communications campaign was effective, with heightened interest in clinical trial participation generated within the community. Strong social media engagement and digital efforts resulted in increased trial website views, and community education and awareness efforts resulted in increased clinicaltrials.gov views to an average of 2-3 clicks per day. Approximately 278,000 users visited the RISE UP website and the campaign's YouTube video, which launched on World Sickle Cell Day has attracted 3 million views since Q4 2022. Conclusion: To meet the needs of the SCD pt and caregiver community and advance clinical trial research, we implemented a patient-centered approach to clinical trial protocol design and trial recruitment. Overall, this patient-centric approach could be useful in improving community engagement, designing trials that better reflect the needs and concerns of the pt population, and ultimately improving pt participation and diverse representation in clinical trials.

The Glass Wall: Gendered Authorship Disparities in in CD 19 and BCMA CAR-T Clinical Trials for Lymphoma and Myeloma

Introduction: Existing literature suggests that women are significantly underrepresented in the field of hematology-oncology. Data from 2021 suggests that women make up 35.6% of hematologists, and thus the disparity continues in clinical trial research authorship. Minorities including women receive fewer awards, deliver fewer board review lectures, and hold fewer professorships, and leadership positions in clinical departments and professional organizations. To further investigate this issue, we conducted a study to assess the gender gap in authorship across 13 pivotal clinical trials that led to the approval of CD19 and BCMA Chimeric antigen receptor T cell (CAR-T) therapies. Methods: We included the 13 pivotal trials that led to the approval of CART for Acute Lymphoblastic leukemia (ALL), lymphoma and myeloma , published between 2017-2022. These included the trials: ELIANA, ZUMA-1, JULIET, ZUMA-2, KarMMa, TRANSCEND, ZUMA-5, CARTITUDE-1, ZUMA-7, ZUMA-3, TRANSFORM, PILOT, and ELARA. We examined the overall number of female authors, the number of lead female authors as defined as first, second, or last author, and the ratio of all authors to female authors. 367 total authors were included in the analysis, with several authors being included more than once for their work on separate studies. Results: Table 1 summarizes the results. Of the 367 authors assessed, 109 were female, correlating to 28.9% female authorship. The only study with female authorship >50% was ELIANA, a 2017 pediatric study, while all others had >50% male authorship. 7 (54%) of the 13 studies had females as lead authors; of note, 6 out of 7 of these studies were published after 2021. Conclusion: Gender inequities in research authorship are pervasive in many areas of medicine, including the field of immune effector cell therapy. Publications in the field broadly are overwhelmingly male dominated, possibly reflective of lower female representation in transplant and cellular therapy. Despite this, we observed improved gender equality in authorship in more recent publications since 2021, and in certain research areas such as pediatric hematology-oncology. Recognizing these seemingly invisible barriers is the first step in bringing gender equity to the field of hematopoietic stem cell transplant and cellular therapy, with gender serving as one of many domains in which underrepresented groups' ability to scale the glass wall must be supported. Table 1.

Radiotherapy in the preoperative neoadjuvant treatment of locally advanced rectal cancer.

Radiotherapy and chemotherapy are effective treatments for patients with locally advanced rectal cancer (LARC) and can significantly improve the likelihood of R0 resection. Radiotherapy can be used as a local treatment to reduce the size of the tumor, improve the success rate of surgery and reduce the residual cancer cells after surgery. Early chemotherapy can also downgrade the tumor and eliminate micrometastases throughout the body, reducing the risk of recurrence and metastasis. The advent of neoadjuvant concurrent radiotherapy (nCRT) and total neoadjuvant treatment (TNT) has brought substantial clinical benefits to patients with LARC. Even so, given increasing demand for organ preservation and quality of life and the disease becoming increasingly younger in its incidence profile, there is a need to further explore new neoadjuvant treatment options to further improve tumor remission rates and provide other opportunities for patients to choose watch-and-wait (W&W) strategies that avoid surgery. Targeted drugs and immunologic agents (ICIs) have shown good efficacy in patients with advanced rectal cancer but have not been commonly used in neoadjuvant therapy for patients with LARC. In this paper, we review several aspects of neoadjuvant therapy, including radiation therapy and chemotherapy drugs, immune drugs and targeted drugs used in combination with neoadjuvant therapy, with the aim of providing direction and thoughtful perspectives for LARC clinical treatment and research trials.

Electronic health records (EHRs) in clinical research and platform trials: Application of the innovative EHR-based methods developed by EU-PEARL

ObjectiveElectronic Health Record (EHR) systems are digital platforms in clinical practice used to collect patients’ clinical information related to their health status and represents a useful storage of real-world data. EHRs have a potential role in research studies, in particular, in platform trials. Platform trials are innovative trial designs including multiple trial arms (conducted simultaneously and/or sequentially) on different treatments under a single master protocol. However, the use of EHRs in research comes with important challenges such as incompleteness of records and the need to translate trial eligibility criteria into interoperable queries. In this paper, we aim to review and to describe our proposed innovative methods to tackle some of the most important challenges identified. This work is part of the Innovative Medicines Initiative (IMI) EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project’s work package 3 (WP3), whose objective is to deliver tools and guidance for EHR-based protocol feasibility assessment, clinical site selection, and patient pre-screening in platform trials, investing in the building of a data-driven clinical network framework that can execute these complex innovative designs for which feasibility assessments are critically important. MethodsISO standards and relevant references informed a readiness survey, producing 354 criteria with corresponding questions selected and harmonised through a 7-round scoring process (0–1) in stakeholder meetings, with 85% of consensus being the threshold of acceptance for a criterium/question. ATLAS cohort definition and Cohort Diagnostics were mainly used to create the trial feasibility eligibility (I/E) criteria as executable interoperable queries. ResultsThe WP3/EU-PEARL group developed a readiness survey (eSurvey) for an efficient selection of clinical sites with suitable EHRs, consisting of yes-or-no questions, and a set-up of interoperable proxy queries using physicians’ defined trial criteria. Both actions facilitate recruiting trial participants and alignment between study costs/timelines and data-driven recruitment potential. ConclusionThe eSurvey will help create an archive of clinical sites with mature EHR systems suitable to participate in clinical trials/platform trials, and the interoperable proxy queries of trial eligibility criteria will help identify the number of potential participants. Ultimately, these tools will contribute to the production of EHR-based protocol design.

Effect of abnormal body weight on mortality and functional recovery in adults after stroke: An umbrella review.

Several published systematic reviews have drawn conflicting conclusions on the effect of abnormal body weight (i.e. being underweight, overweight or obese) on outcomes following stroke. The 'obesity paradox' seen in several diseases (wherein obesity, often associated with mortality and morbidity, appears to be protective and improve outcomes) may be evident after stroke, but inconsistent results of existing reviews, and the issue of being underweight, are worth investigating further. To better understand the impact of body weight on prognosis after stroke, we aimed to answer the following research question: What is the effect of abnormal body weight (underweight, overweight, or obesity) on mortality and functional recovery in adults after stroke? We conducted an umbrella review to synthesize existing evidence on the effects of abnormal body weight on stroke outcomes. We searched Cumulated Index to Nursing and Allied Health Literature (CINAHL) Complete, COCHRANE Database of Systematic Reviews, PubMed, Medline, PEDro, and EMBASE Classic + EMBASE, from inception until 28 February 2023. Seven systematic reviews (1,136,929 participants) from 184 primary studies (counting duplicates) were included. While the risk of mortality increases with being underweight (body mass index (BMI) < 18.5 kg/m2), excess body weight (being overweight (BMI = 25-29.9 kg/m2) or obese (BMI > 30 kg/m2)) is associated with reduced mortality. The impact of abnormal body weight on functional recovery is less clear; data from studies of being underweight are associated with poor functional outcomes while those from studies of excess body weight are inconclusive. Abnormal body weight effects post-stroke outcomes and should be considered in clinical decision-making, prognostic research, and clinical trials of rehabilitation interventions. The "obesity paradox" is evident after stroke, and excess body weight is associated with reduced mortality compared to normal body weight. It is recommended that body weight is routinely recorded for stroke patients, and further research, including well-designed cohort studies with reliable weight data, is needed to further investigate the impact of body weight and distribution on post-stroke outcomes.

Harmonization of multi-site diffusion tensor imaging data for cervical and thoracic spinal cord at 1.5T and 3T using longitudinal ComBat.

MRI scanner hardware, field strengths, and sequence parameters are major variables in diffusion studies of the spinal cord. Reliability between scanners is not well known, particularly for the thoracic cord. DTI data was collected for the entire cervical and thoracic spinal cord in thirty healthy adult subjects with different MR vendors and field strengths. DTI metrics were extracted and averaged for all slices within each vertebral level. Metrics were examined for variability and then harmonized using longitudinal ComBat (longComBat). Four scanners were used: Siemens 3T Prisma, Siemens 1.5T Avanto, Philips 3T Ingenia, Philips 1.5T Achieva. Average full cord diffusion values/standard deviation for all subjects and scanners were FA: 0.63, σ = 0.10, MD: 1.11, σ = 0.12 × 10-3 mm2/s, AD: 1.98, σ = 0.55 × 10-3 mm2/s, RD: 0.67, σ = 0.31 × 10-3 mm2/s. FA metrics averaged for all subjects by level were relatively consistent across scanners, but large variability was found in diffusivity measures. Coefficients of variation were lowest in the cervical region, and relatively lower for FA than diffusivity measures. Harmonized metrics showed greatly improved agreement between scanners. Variability in DTI of the spinal cord arises from scanner hardware differences, pulse sequence differences, physiological motion, and subject compliance. The use of longComBat resulted in large improvement in agreement of all DTI metrics between scanners. This study shows the importance of harmonization of diffusion data in the spinal cord and potential for longitudinal and multisite clinical research and clinical trials.

The impact of COVID-19 on clinical research: the PIPPRA and MEDRA experience.

Coronavirus disease 2019 (COVID-19) has had a significant impact on clinical research. This paper aims to provide an insight into how the COVID-19 pandemic, associated public health restrictions and international guidance on the conduct of clinical research impacted two clinical rheumatology research trials - the Physiotherapist-led Intervention to Promote Physical Activity in Rheumatoid Arthritis (PIPPRA) and the MEDiterranean diet in Rheumatoid Arthritis (MEDRA) projects. The March 2019 public health restrictions imposed to mitigate the risk of COVID-19 occurred at a time when PIPPRA was in the process of delivering assessment and intervention on a face-to-face basis (n=48) and MEDRA had commenced recruitment. Participants in PIPPRA and MEDRA had a diagnosis of rheumatoid arthritis, with some being immunosuppressed and thus at a higher risk for COVID-19. The decision-making processes of both trials is outlined to demonstrate the required amendments to continue in the context of the COVID-19 pandemic. Amendments to PIPPRA and MEDRA trial protocols were agreed and received ethical and funder approval. Both trials switched from a face-to-face delivery to a telehealth using online platforms. The PIPPRA study was paused for five months (April-August 2020), resulting in n=33 (60%) negative deviations from assessment protocol. MEDRA switched from face-to-face to online recruitment with 20% (n=35/44) negative deviations in recruitment. Of the n=18 participants who consented to participating in a face-to-face trial, just n=2 (11%) opted to engage with telehealth delivery of the intervention. MEDRA assessment and intervention deviations were 100% as no sessions were completed as planned in 2020. The COVID-19 pandemic has severely impacted the PIPPRA and MEDRA clinical trials. Moving face-to-face clinical research to telehealth delivery may not be the panacea it is purported to be. Our experiences may be of benefit to researchers, clinicians, and funders in seeking to continue clinical research during a global pandemic.

APOE Genotype and Alzheimer Disease Risk Across Age, Sex, and Population Ancestry

Apolipoprotein E (APOE)*2 and APOE*4 are, respectively, the strongest protective and risk-increasing, common genetic variants for late-onset Alzheimer disease (AD), making APOE status highly relevant toward clinical trial design and AD research broadly. The associations of APOE genotypes with AD are modulated by age, sex, race and ethnicity, and ancestry, but these associations remain unclear, particularly among racial and ethnic groups understudied in the AD and genetics research fields. To assess the stratified associations of APOE genotypes with AD risk across sex, age, race and ethnicity, and global population ancestry. This genetic association study included case-control, family-based, population-based, and longitudinal AD-related cohorts that recruited referred and volunteer participants. Data were analyzed between March 2022 and April 2023. Genetic data were available from high-density, single-nucleotide variant microarrays, exome microarrays, and whole-exome and whole-genome sequencing. Summary statistics were ascertained from published AD genetic studies. The main outcomes were risk for AD (odds ratios [ORs]) and risk of conversion to AD (hazard ratios [HRs]), with 95% CIs. Risk for AD was evaluated through case-control logistic regression analyses. Risk of conversion to AD was evaluated through Cox proportional hazards regression survival analyses. Among 68 756 unique individuals, analyses included 21 852 East Asian (demographic data not available), 5738 Hispanic (68.2% female; mean [SD] age, 75.4 [8.8] years), 7145 non-Hispanic Black (hereafter referred to as Black) (70.8% female; mean [SD] age, 78.4 [8.2] years), and 34 021 non-Hispanic White (hereafter referred to as White) (59.3% female; mean [SD] age, 77.0 [9.1] years) individuals. There was a general, stepwise pattern of ORs for APOE*4 genotypes and AD risk across race and ethnicity groups. Odds ratios for APOE*34 and AD risk attenuated following East Asian (OR, 4.54; 95% CI, 3.99-5.17),White (OR, 3.46; 95% CI, 3.27-3.65), Black (OR, 2.18; 95% CI, 1.90-2.49) and Hispanic (OR, 1.90; 95% CI, 1.65-2.18) individuals. Similarly, ORs for APOE*22+23 and AD risk attenuated following White (OR, 0.53, 95% CI, 0.48-0.58), Black (OR, 0.69, 95% CI, 0.57-0.84), and Hispanic (OR, 0.89; 95% CI, 0.72-1.10) individuals, with no association for Hispanic individuals. Deviating from the global pattern of ORs, APOE*22+23 was not associated with AD risk in East Asian individuals (OR, 0.97; 95% CI, 0.77-1.23). Global population ancestry could not explain why Hispanic individuals showed APOE associations with less pronounced AD risk compared with Black and White individuals. Within Black individuals, decreased global African ancestry or increased global European ancestry showed a pattern of APOE*4 dosage associated with increasing AD risk, but no such pattern was apparent for APOE*2 dosage with AD risk. The sex-by-age-specific interaction effect of APOE*34 among White individuals (higher risk in women) was reproduced but shifted to ages 60 to 70 years (OR, 1.48; 95% CI, 1.10-2.01) and was additionally replicated in a meta-analysis of Black individuals and Hispanic individuals (OR, 1.72; 95% CI, 1.01-2.94). Through recent advances in AD-related genetic cohorts, this study provided the largest-to-date overview of the association of APOE with AD risk across age, sex, race and ethnicity, and population ancestry. These novel insights are critical to guide AD clinical trial design and research.