Investigator-initiated Trials Research Articles

Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design.

Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration's marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs' efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

Abstract PO3-09-10: Minority participation in breast cancer therapeutic trials at an NCI-CCC affiliated safety-net system: Advancing equity in clinical research

Abstract Authors: Nasir Qureshi, MBBS Fabian Robles, MS Mai Badran, MBBS Nisha Unni, MD Hsiao C Li, MD Samira Syed, MD Glenda Delgado-Ramos, MD Sangeetha Reddy, MD Heather McArthur, MD Navid Sadeghi, MD Title: Minority participation in breast cancer therapeutic trials at an NCI-CCC affiliated safety-net system: Advancing equity in clinical research. Introduction: Participation of under-represented minorities (URMs) in clinical trials enhances the generalizability of the findings and can also improve clinical outcomes. Multiple factors, such as access, language barrier, distrust, and misconceptions, negatively impact URM enrollments in cancer clinical trials. Here we describe our approach to increase participation of breast cancer URMs in therapeutic trials at an academic-affiliated safety-net system. Methods: Parkland Health (PH) is a large safety-net system in Dallas County, Texas, and is affiliated with the NCI-CCC designated Harold C. Simmons Comprehensive Cancer Center (SCCC) at UT Southwestern. A dedicated team of SCCC research coordinators support the clinical trial operations at PH. In 2020, several steps were taken to increase access and enrollment of URMs in breast cancer trials at PH including review and optimization of the trial portfolio (more trials in curative intent setting), proactive screening, increasing provider awareness, and addition of a bilingual (English/Spanish) patient navigator to the research team. Data for 2018-2019 (pre-intervention) and 2021-2022 (post-intervention) is presented here. Data for 2020 is excluded due to the impact of COVID-19 pandemic on trial operations. Results: Racial and ethnic minorities composed the majority of breast cancer patients at PH (52% Hispanics, 32% Blacks). Ten percent of new patients at PH presented with metastatic disease. In 2018-2019, PH's portfolio included 13 therapeutic trials, 5 of which (38%) were in metastatic setting and 3 required a biomarker. A total of 47 breast cancer patients were enrolled in 11 therapeutic trials at PH, accounting for an average annual accrual rate of 6.1% (7.6% in 2018 and 4.5% in 2019). Accrual to trials in the metastatic setting accounted for 11% (5/47) of enrollments. Two trials in the metastatic setting had zero accruals. In 2021-2022, 16 trials were open at PH, including 7 cooperative group, 4 industry-sponsored (ISTs), and 5 Investigator-Initiated trials (IITs). Five trials (31%) were in metastatic setting and 4 required a genomic biomarker. A total of 87 patients were enrolled in 2021-22, representing an 85% increase in the accruals over the baseline (2018-2019). The annual accrual rates for 2021 and 2022 were 10.5% (43/409) and 10.4% (44/423), respectively. In 2021-22, 63 were enrolled in cooperative group studies, 20 in IITs, and 4 in ISTs. Accrual to trials in the metastatic setting accounted for 6% (5/87) of enrollments. Two studies had zero accruals. The majority of the trial participants (77/87; 89%) belonged to URMs (64 Hispanic, 13 Black). Overall participation rate was 67% (87/129) and was significantly higher in Hispanics compared to Blacks (77% vs 41% - p < 0.001). Among Black patients who declined participation, 42% (8/19) cited lack of interest as the reason, which may reflect distrust or misperceptions regarding clinical trials. Conclusions: The collaboration between academic centers and safety-net systems provides a unique opportunity to promote equity in clinical trials by increasing access and enrollment of URMs. Developing a balanced portfolio that matches the patient population, enhanced screening, and incorporating clinical trial patient navigation at our institution resulted in a sustained increase in the number of URM trial participants. Given the lower participation rate among eligible Black patients, we aim to expand our clinical trial navigation program to better address the distrust and misperceptions regarding clinical trials, as a strategy to further improve trial participation at our institution. Citation Format: Nasir Qureshi, Fabian Robles. Minority participation in breast cancer therapeutic trials at an NCI-CCC affiliated safety-net system: Advancing equity in clinical research [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-10.

Abstract PO5-26-11: The Breast Cancer Research Foundation Drug Research Collaborative – A unique and innovative model for industry-funded, academically driven research to advance the field of breast cancer

Abstract The Breast Cancer Research Foundation (BCRF) is committed to preventing and curing breast cancer through groundbreaking research. In pursuit of this mission, the BCRF launched the Drug Research Collaborative (DRC) in 2016—a pioneering program designed to bridge the gap between academic investigators and access to investigational therapies, thereby fostering greater academic-driven research in breast cancer. The DRC's primary objective is to fund independent, innovative, and high-quality investigator-initiated trials (IITs) and pre-clinical/translational research projects. In conventional drug development, industry-sponsored registration trials play a crucial role, leaving limited resources and scope for exploratory and translational IITs that fall outside the industry's drug approval strategy. Additionally, industry-funded IIT research faces challenges such as reputational risks, perceived influence during internal review processes, intellectual property (IP) concerns, and logistics/program management burdens. The BCRF-DRC program addresses these challenges by issuing requests for proposals to generate creative and unbiased ideas, which are then vetted through an academic review process involving leading breast cancer experts. The most promising research projects are selected for further advancement. The BCRF-DRC program is facilitated by the BCRF research staff, providing project management, while the Translational Breast Cancer Research Consortium (TBCRC), founded by the BCRF and also supported by Susan G. Komen, supports the clinical trial aspects of the program. Since its inception, the BCRF-DRC has expanded from one to three industry partners, securing a total funding of $25 million for 15 projects, including seven clinical trials and eight pre-clinical projects. This abstract reports on the ongoing progress and outcomes achieved by these three programs. The BCRF-DRC represents a revolutionary paradigm in research funding and collaboration by harnessing the collective power of industry partners, philanthropic organizations, and academic institutions. Through this collaborative effort, the BCRF-DRC provides a unique platform for researchers to accelerate the translation of scientific discoveries into effective clinical interventions, thus making significant strides in the field of breast cancer in the coming decades. By empowering academic investigators, fostering unbiased research, and addressing the limitations of industry-funded IITs, the BCRF-DRC is revolutionizing breast cancer research and driving the development of novel interventions. This abstract highlights the transformative potential of the BCRF-DRC program and its contribution to advancing breast cancer treatments and ultimately improving patient outcomes. The success of this collaborative model serves as a testament to the power of multi-sector partnerships and the pivotal role they play in shaping the future of breast cancer research. Citation Format: Unnati Jariwala, Dorraya El-Ashry, Judy Garber, Larry Norton. The Breast Cancer Research Foundation Drug Research Collaborative – A unique and innovative model for industry-funded, academically driven research to advance the field of breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-26-11.

74 Trial-CARE: Centralized Support Services for Investigator-Initiated Multi-Site Clinical Trials

OBJECTIVES/GOALS: To describe the impact of Trial-CARE (Coordination, Acceleration, and Recruitment Enhancement), a centralized service core at Washington University (WU), aimed at enhancing the capability of investigator-initiated multi-site clinical trials at WU and partner CTSA institutions. METHODS/STUDY POPULATION: Through review of our marketing materials and service tracking system we defined the following Trial-CARE offerings: Infrastructure: Trial-CARE is a centralized service core at WU. Whereby, a team member is sourced to an investigator-initiated multi-site clinical trial (II-MCT) to ensure the achievement of study milestones across any phase of the clinical trial life cycle. Team: Our team consists of research professionals with expertise in II-MCT project management, data management, and administrative/regulatory management. Services: * One free 60-minute case consultation * Tiers of Service * Academic Research Organization (ARO) support * Clinical Coordinating Center * Data Coordinating Center * II-MCT project management support * Time-limited targeted support RESULTS/ANTICIPATED RESULTS: Trial-CARE has completed 94 consultations in support of WU and partner CTSA institutions enabling the streamlining of study start-up; guidance for study recruitment, implementation, and operations; and offering resources to foster career development. Consultations can be completed at any phase in the clinical trial lifecycle, with Trial-CARE completing: * 12% in the idea phase * 45% in the grant development and submission stage * 28% after funding has been awarded Top reasons researchers connect with Trial-CARE about II-MCTs: * regulatory guidance (40%) * general information about Trial-CARE Services and II-MCTs (35%) * protocol development (21%) * data management (20%) * study budgeting (20%) DISCUSSION/SIGNIFICANCE: In response to a WU wide survey, Trial-CARE plans to generate informational webinars and is creating a clinical trial tracking dashboard, to pro-actively offer support services to researchers prior to grant funding. The goal is also to increase the percentage of consultations completed in the idea phase and the grant development and submission stage.

A systematic review and meta-analysis of randomized controlled head-to-head trials of recommended drugs for neuropathic pain

Abstract Neuropathic pain is a challenging chronic pain condition. Limited knowledge exists regarding the relative effectiveness of pharmacological treatments, and differences in trial design and impact of the placebo response preclude indirect comparisons of efficacy between drug classes. The purpose of this systematic review and meta-analysis of head-to-head trials was to compare the efficacy and tolerability of drugs recommended for neuropathic pain. We conducted a systematic review and meta-analysis of direct-comparison double-blind randomized trials. Primary outcomes were mean change in pain intensity and number of responders with a 50% reduction in pain intensity. Secondary outcomes encompassed quality of life, sleep, emotional functioning, and number of dropouts because of adverse events. We included 30 trials (4087 patients), comprising 16 crossover and 14 parallel-group design studies. All studies were conducted in adults, and the majority were investigator-initiated trials. We found moderate-quality evidence for equivalence (no clinically relevant difference) between tricyclic antidepressants (TCA) and gabapentin/pregabalin with a combined mean difference in pain score of 0.10 (95% CI −0.13 to 0.32). We could not document differences between TCA and serotonin–noradrenaline reuptake inhibitors (SNRI), between SNRI and gabapentin/pregabalin, or between opioids and TCA (low quality of evidence). We found more dropouts because of adverse events with SNRI and opioids compared with TCA (low quality of evidence). We did not identify any studies that included topical treatments. This systematic review of direct-comparison studies found evidence for equivalence between TCA and gabapentin/pregabalin and fewer dropouts with TCA than SNRI and opioids.

Abstract 2585: First in human study with a novel peptide binder to glypican-3, demonstrates high specificity as a PET imaging agent in patients with hepatocellular carcinoma

Abstract Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The American Association for the Study of Liver Disease recommends surveillance for high-risk individuals with abdominal ultrasound, triple phase contrast CT or MRI. However, these imaging techniques have limited sensitivity in classifying lesions smaller than 2 centimeters. The use of [18F]FDG Positron Emission Tomography (PET) is constrained due to insufficient uptake by HCC lesions over background liver uptake. Hence, there is an urgent need for more precise radiotracers for HCC. This study introduces the development of a novel radiotracer that binds to glypican-3 (GPC3), a cell membrane-anchored oncofetal protein overexpressed in HCC with minimal normal tissue expression. Methods: [68Ga]Ga-RYZ-GPC3 is composed of a small macrocyclic peptide binder with high affinity to GPC3 linked with a tetraxetan moiety capable of chelating a variety of radioisotopes including positron-emitting 68Ga and other radiometals. The unlabeled binder to GPC3 was synthesized by the sponsor and provided to three imaging centers in India as part of investigator-initiated trials reviewed and approved by each site’s institutional review board and ethics committee. Labeling with 68Ga and quality checks of the product was performed locally at each center. Patients with high clinical suspicion or with confirmed HCC who gave informed consent received injections of 1.5-5.5 mCi of [68Ga]Ga-RYZ-GPC3 and underwent PET-CT scanning at predetermined intervals. Some patients underwent companion [18F]FDG PET-CT scans in accordance with local guidelines. Results: A total of 64 patients underwent [68Ga]Ga-RYZ-GPC3 PET-CT scans. The median age within the cohort was 61 (41-83), 22% were female. Liver cirrhosis was present in 72% of patients, attributed to hepatitis B, hepatitis C or NASH in 17%, 13% and 20% of cases. Notably, 92% of patients exhibited at least one positive lesion on [68Ga]Ga-RYZ-GPC3 scans. The median SUVmax of GPC3-avid liver lesions was 15.5 (range 1.1 to 137.0) while the median liver SUVmean was 1.6 (0.3-7.9). Physiologic uptake was predominantly observed in the kidneys, the primary route of clearance, with a median SUVmean of 10.9 (2.2-20.7). Additionally, 20 patients underwent [18F]FDG PET-CT scan for comparison. The median SUVmax of lesions on 68Ga-RYZ-GPC3 vs [18F]FDG PET was 11.0 (1.1-137.0) vs 3.8 (1.2-12.2). Conclusion: Early human imaging results in patients with HCC indicate that [68Ga]Ga-RYZ-GPC3 has high tumor lesion specificity compared to normal liverand demonstrates the potential of [68Ga]Ga-RYZ-GPC3 to improve detection of HCC over conventional [18F]FDG PET-CT. In addition, the binder could be complexed with a therapeutic radioisotope as a novel targeted therapeutic option for HCC. Further investigation of this first-in-class binder to HCC is warranted. Citation Format: Chandresakhar Bal, Sanjana Ballal, Kumar Kallur, Anna Karmann, Ye Yuan, Jessica Rearden, Kathryn Shah, Charlotte Lorenz, Susan Moran, Ken Song, Ishita Sen. First in human study with a novel peptide binder to glypican-3, demonstrates high specificity as a PET imaging agent in patients with hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2585.

Operational Differences between Product Development Partnership, Pharmaceutical Industry, and Investigator Initiated Clinical Trials.

Medicine development is a lengthy endeavour. Increasing regulatory stringency and trial complexity might lead to reduced efficiency, dwindled output, and elevated costs. However, alternative models are possible. We compared the operational differences between pharmaceutical industry sponsored trials, product development partnership trials, and investigator-initiated trials to identify key drivers of inefficiency in clinical research. We conducted an exploratory mixed-methods study with stakeholders, including clinical trial sponsors, contract research organisations, and investigators. The qualitative component included 40 semi-structured interviews, document reviews of 12 studies and observations through work shadowing in research institutions in Burkina Faso, Mali, and Switzerland. The findings were triangulated with an online survey polling clinical research professionals. The operational differences were grouped under five categories: (i) trial start-up differences including governance and management structure; (ii) study complexity; (iii) site structural and organisational differences; (iv) study conduct, quality approaches, and standard operating procedures; and (v) site capacity strengthening and collaboration. Early involvement of sites in the planning and tailored quality approaches were considered critical for clinical operations performance. Differences between the types of trials reviewed pertained to planning, operational complexities, quality approaches, and support to the sites. Integration of quality-by-design components has the potential to alleviate unnecessary process burden.

Nasal spray of an IgM-like ACE2 fusion protein HH-120 prevents SARS-CoV-2 infection: Two investigator-initiated postexposure prophylaxis trials.

HH-120, an IgM-like angiotensin converting enzyme 2 (ACE2) fusion protein, has been developed as a nasal spray against Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) and is currently undergoing human trials.HH-120 nasal spray was assessed for postexposure prophylaxis (PEP) in two investigator-initiated (NS01 and NS02) trials with different risk levels of SARS-CoV-2 exposure. NS01 enrolled family caregiver participants who had continuous contacts with laboratory-confirmed index cases; NS02 enrolled participants who had general contacts (Part 1) or close contacts (Part 2) with index cases. The primary endpoints were safety and laboratory-confirmed and/or symptomatic SARS-CoV-2 infection.In NS01 trial (14 participants), the SARS-CoV-2 infection rates were 25% in the HH-120 group and 83.3% in the external control group (relative risk reduction [RRR]:70.0%). In NS02-Part 1 (193 participants), the infection rates were 4% (HH-120) versus 11.3% (placebo), symptomatic infection rates were 0.8% versus 3.5%, hence with a RRR of 64.6% and 77.1%, respectively. In Part 2 (76 participants), the infection rates were 17.1% (HH-120) versus 30.4% (placebo), symptomatic infection rates were 7.5% versus 27.3%, with a RRR of 43.8% and 72.5%, respectively. No HH-120-related serious adverse effects were observed.The HH-120 nasal spray used as PEP was safe and effective in preventing laboratory-confirmed and symptomatic SARS-CoV-2 infection.

Development of clinical trials for non-small cell lung cancer drugs in China from 2005 to 2023.

Over the past few decades, the development of anti-cancer drugs in China has made outstanding achievements based on the support of national policies. To assess the progress of non-small cell lung cancer (NSCLC) drugs, we conducted a statistical analysis of clinical trials of drugs targeting NSCLC in China from 2005 to 2023. We downloaded, screened and analysed the data from three official websites, the Centre for Drug Evaluation of China National Medical Products Administration website (NMPA), ClinicalTrials.gov and the Chinese Clinical Trial Registry (ChiCTR). From January 1, 2005 to April 15, 2023, a total of 1,357 drug clinical trials that met the standards were included, and the number of registered drug clinical trials has been increasing year by year, reaching the maximum of 199 in 2021. Among them, the maximum of 462 items (34.05%) in phase II clinical trials, followed by 333 (24.54%) in phase III clinical trials, and 139 (10.24%) in phase IV clinical trials. In all drug clinical trials, industry sponsored trials (ISTs) have 722 items (53.21%), which are higher than investigator-initiated trials (IITs). The clinical trials of chemical drugs have a maximum of 723 items (53.28%), while biopharmaceuticals have grown rapidly in the past 10 years, with a total of 374 (27.56%), and 48.19% of the drug clinical trials of combined medication. In addition, the geographical distribution of the leading units and participating units of Chinese drug clinical trials are uneven, and economic regions such as Beijing, Shanghai, Jiangsu are obviously ahead of other regions. From 2005 to 2023, the clinical trials of registered drugs for the treatment of NSCLC increased rapidly. Among them, due to the development of immunotherapy, the clinical trials of biopharmaceuticals and drugs for combined medication are growing most rapidly, while the exploration of the original drugs is a little far from enough. Our research provides a direction for the future drug clinical trials of NSCLC, laying foundation for further extending the survival rate of patients with NSCLC.

Activities critical to success and growth of clinical trials networks. What is needed and how are we doing? An Australian and New Zealand perspective

BackgroundClinical trial evidence underpins evidence-based medicine and the improvement of healthcare worldwide. In Australasia, a significant proportion of clinical trials are conducted by geographically dispersed and multidisciplinary clinical researchers under the auspices of Clinical Trials Networks (CTNs). These groups play an important role in contributing to evidence-based medicine, primarily by conducting investigator-initiated clinical trials. Despite their clear benefits in terms of return on investment, CTNs suffer significant challenges.MethodsWe conducted surveys and focus groups with Australian and New Zealand CTNs to identifying the activities and attributes that enable CTNs to operate successfully. Based on our findings, we then conducted further surveys of Australian and New Zealand CTNs to identify the prevalence of these success factors in existing CTNs.ResultsOur focus groups identified three key themes associated with success and growth of a CTN: engaged membership, established infrastructure, and sustainability; and thirteen critical success factors: shared vision and motivation; strong leaders, governance and succession planning; an executive officer; sustainable funding for operations; effective communication; diverse representation and consumer input; transparent processes; a strong pipeline of trials; a reputable and recognised CTN brand; innovation and adaption; an effective group of network sites with a skilled workforce; embedded trials and prioritisation of research. These key themes and the relevant key areas were presented to 30 CTNs. Two factors were almost universally present in CTNs, reflecting the importance of these attributes: the presence of an executive officer, and a strong pipeline of trials. Three factors had a particularly low prevalence: sustainable funding for operations, effective communication, and embedded trials.ConclusionsBy supporting both emerging and established CTNs to achieve critical success factors, we can improve the efficiency of CTNs to continue to contribute and expand their clinical trial activities. Particular focus needs to be on finding sustainable funding for CTNs, and raising awareness of the critical role undertaken by CTNs to improve healthcare and health outcomes.

Clinical trial implementation: a primer for neurosurgeons.

In the current landscape of evidence-based medicine, prospective clinical trials are an important avenue through which to establish the efficacy and safety of biomedical treatments compared with standard-of-care interventions. Depending on their scope and aims, clinical trials can be extremely costly and time intensive, and significant coordination is needed to ensure optimal utilization of healthcare resources, adherence to the principles of biomedical ethics, and appropriate interpretation of study results. This review highlights the core principles for designing and implementing clinical trials within neurosurgery, with the aim to provide clinicians with a framework for implementing both investigator-initiated and industry-sponsored trials.

Toward a global harmonization of service infrastructure in academic clinical trial units: an international survey.

Clinicians around the world perform clinical research in addition to their high workload. To meet the demands of high quality Investigator Initiated Trials (IITs), Clinical Trial Units (CTUs) (as part of Academic Research Institutions) are implemented worldwide. CTUs increasingly hold a key position in facilitating the international mutual acceptance of clinical research data by promoting clinical research practices and infrastructure according to international standards. In this project, we aimed to identify services that established and internationally operating CTUs - members of the International Clinical Trial Center Network (ICN) - consider most important to ensure the smooth processing of a clinical trial while meeting international standards. We thereby aim to drive international harmonization by providing emerging and growing CTUs with a resource for informed service range set-up. Following the AMEE Guide, we developed a questionnaire, addressing the perceived importance of different CTU services. Survey participants were senior representatives of CTUs and part of the ICN with long-term experience in their field and institution. Services concerning quality and coordination of a research project were considered to be most essential, i.e., Quality management, Monitoring and Project management, followed by Regulatory & Legal affairs, Education & Training, and Data management. Operative services for conducting a research project, i.e., Study Nurse with patient contact and Study Nurse without patient contact, were considered to be least important. To balance the range of services offered while meeting high international standards of clinical research, emerging CTUs should focus on offering (quality) management services and expertise in regulatory and legal affairs. Additionally, education and training services are required to ensure clinicians are well trained on GCP and legislation. CTUs should evaluate whether the expertise and resources are available to offer operative services.

Experience for registration of investigator-initiated clinical trials

Experience for registration of investigator-initiated clinical trials

Demographic reporting and language exclusion in gynecologic oncology clinical trials

Participation in clinical trials may help mitigate disparate cancer outcomes. Thus, ensuring equitable access to clinical trials is a major priority for national cancer organizations. This study aimed to examine clinical trial eligibility criteria that may adversely affect the enrollment of underrepresented groups and assess the availability of demographic information in published gynecologic oncology studies. ClinicalTrials.gov was searched for gynecologic oncology studies conducted between 1997 and 2021. Each study's inclusion and exclusion criteria were reviewed to determine whether demographic factors were used for enrollment screening. For published studies, demographic variables that were reported were identified. The expected clinical trial enrollment based on disease incidence and mortality was compared with the observed trial enrollment based on race. There were 1597 gynecologic oncology studies: 883 (55%) from ovarian cancer studies, 336 (21%) from cervical cancer studies, 262 (17%) from uterine cancer studies, and 116 (7%) from multisite gynecologic oncology studies. Of the 581 published studies, 554 (95%) reported age, 363 (63%) reported race, and 171 (29%) reported ethnicities. Cervical cancer studies were most likely to report demographic information, including race (P=.026) and ethnicity (P<.001). During the study period, 189 studies (12%) excluded patients based on the language spoken. Industry-sponsored trials (odds ratio, 0.07; 95% confidence interval, 0.02-0.30) and organization-sponsored trials (odds ratio, 0.40; 95% confidence interval, 0.22-0.73) were less likely to exclude patients because of language than investigator-initiated trials. A minority of patients (37%) in cervical cancer trials were of White race, compared with 85% of patients in uterine cancer trials and 82% of patients in ovarian cancer trials. Over the last 3 decades, 1 in 10 gynecologic oncology trials excluded patients because of language. Race and ethnicity were reported in more than half of the available studies. Initiatives to increase transparency in recruiting underrepresented patients and reporting demographic data are urgently needed.

Preventing Potential Patient Harm Through Clinical Content Interventions During Oncology Clinical Trial Implementation.

Clinical trial documents are complex and may have inconsistencies, leading to potential site implementation errors and may compromise participant safety. This study characterizes the frequency and type of administrative and potential patient safety interventions (PPSIs) made during the review of oncology trial documents for clinical trial implementation by centralized clinical content specialists. A dedicated group of centralized clinical content specialists reviewed trial documents, including the protocol, laboratory manual, and pharmacy/cellular therapy manual, and collected intervention data over a 1-year period. Each trial was categorized by study phase and sponsor type, and multiple interventions could be identified per trial. Interventions were deemed administrative or PPSIs, with PPSIs further subcategorized as medication, laboratory, procedure related, or other. Of 585 clinical trials reviewed, 269 (46%) required intervention(s). Among 1001 interventions, 171 (17.1%) were PPSIs. Most PPSIs were medication related (45.6%), with drug dosing interventions most frequently identified (53.8%). Phase 1 trials had the highest proportion of PPSIs (0.35:1) and administrative interventions (2:1) per trial compared with all other phases. Investigator-initiated trials saw the highest proportion of PPSIs per trial (0.44:1) of all sponsor types. This study demonstrates a gap in patient safety when assessing trial documents for clinical trial implementation. One solution to address this gap is the utilization of a centralized team of clinical specialists to preemptively review trial documents, thereby enhancing patient safety during clinical trial conduct.

The necessity of investigator-initiated trials in Cardiothoracic Surgery.

The necessity of investigator-initiated trials in Cardiothoracic Surgery.

IRB 지속심사와 연구 미준수 연관성 분석

The continuing review of ongoing research approved by the Institutional Review Boards(IRB) is one of the ways to protect human subjects. Though the approval expiration date for new tasks depends on the risk assessment of said task, it is generally limited by law not to exceed a maximum of one year. Continuing review is required to extend the approval expiration date. Through continuing review, the IRB determines whether the research is conducted under the approved protocol, whether any side effects were reported timely, and whether the risk-to-benefit ratio remains favorable. This research used 784 cases of data reviewed by the C University Hospital's clinical research support system from 2019 to 2021 in a retrospective matter and analyzed the characteristics of research and researchers in non-compliance and compliance groups, and types of non-compliances, finding significant differences. Non-compliance groups were highly frequent in investigator initiated trials(IIT), non-clinical trials, and studies without clinical research coordinators, while compliance groups were more frequent in sponsor initiated trials(SIT), studies with co-investigator, and studies with clinical research coordinators. In addition, after analyzing the types of non-compliance, the non-compliance with the IRB reporting and non-compliance with the consent process were high in non-compliance groups. Therefore, we analyzed the relationship between non-compliance and compliance groups in continuing review to find a way to contribute for the ultimate purpose of IRB, protection of human subjects.

Evaluation of Oseltamivir Used to Prevent Hospitalization in Outpatients With Influenza

Despite widespread use, summary evidence from prior meta-analyses has contradictory conclusions regarding whether oseltamivir decreases the risk of hospitalization when given to outpatients. Several large investigator-initiated randomized clinical trials have not yet been meta-analyzed. To assess the efficacy and safety of oseltamivir in preventing hospitalization among influenza-infected adult and adolescent outpatients. PubMed, Ovid MEDLINE, Embase, Europe PubMed Central, Web of Science, Cochrane Central, ClinicalTrials.gov, and WHO International Clinical Trials Registry were searched from inception to January 4, 2022. Included studies were randomized clinical trials comparing oseltamivir vs placebo or nonactive controls in outpatients with confirmed influenza infection. In this systematic review and meta-analysis, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Two independent reviewers (R.H. and É.B.C.) extracted data and assessed risk of bias using the Cochrane Risk of Bias Tool 2.0. Each effect size was pooled using a restricted maximum likelihood random effects model. The quality of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Hospitalization was pooled as risk ratio (RR) and risk difference (RD) estimates with 95% CIs. Of 2352 studies identified, 15 were included. The intention-to-treat infected (ITTi) population was comprised of 6166 individuals with 54.7% prescribed oseltamivir. Across study populations, 53.9% (5610 of 10 471) were female and the mean age was 45.3 (14.5) years. Overall, oseltamivir was not associated with reduced risk of hospitalization within the ITTi population (RR, 0.79; 95% CI, 0.48 to 1.29; RD, -0.17%; 95% CI, -0.23% to 0.48%). Oseltamivir was also not associated with reduced hospitalization in older populations (mean age ≥65 years: RR, 1.01; 95% CI, 0.21 to 4.90) or in patients considered at greater risk of hospitalization (RR, 0.65; 0.33 to 1.28). Within the safety population, oseltamivir was associated with increased nausea (RR, 1.43; 95% CI, 1.13 to 1.82) and vomiting (RR, 1.83; 95% CI, 1.28 to 2.63) but not serious adverse events (RR, 0.71; 95% CI, 0.46 to1.08). In this systematic review and meta-analysis among influenza-infected outpatients, oseltamivir was not associated with a reduced risk of hospitalization but was associated with increased gastrointestinal adverse events. To justify continued use for this purpose, an adequately powered trial in a suitably high-risk population is justified.

CONSENT: Randomized controlled trial of enhanced informed consent compared to standard informed consent to improve patient understanding of early phase oncology clinical trials.

6560 Background: Early phase oncology clinical trials have become increasingly complicated in terms of patient selection and trial procedures. Informed consent has been contentious due to potential ethical issues associated with performing experimental research on patients with advanced cancer who lack standard treatment options. Prior research has shown significant gaps in patient understanding regarding the nature and intent of these trials. CONSENT aimed to test whether enhanced informed consent can improve clinical trial comprehension. Methods: We randomized patients eligible to participate in one of four investigator-initiated early phase oncology clinical trials at the Royal Marsden Drug Development Unit to either a control arm or an experimental arm, stratified by age and educational level. The control arm received the full-length trial PIS, followed by electronic or paper administration of the Quality of Informed Consent Questionnaire Parts A (QuIC-A). The experimental arm received the full-length trial PIS, exposure to a two-page study specific aid and 10 online educational videos (both co-designed with patients and clinicians), followed by administration of the QuIC-A. The primary endpoint was the difference in the QuIC-A score between the control and experimental arm. The accrual target was at least 17 evaluable patients per arm to detect an 8-point difference (80% power, alpha 0.05). Results: 23 patients were accrued to the control arm (17 evaluable) and 22 patients (18 evaluable) were accrued to the experimental arm. Patients were evaluable if they had completed the QuIC-A. 38% of the participants were over the age of 65, 91% identified as White, 56% had completed a university degree and 97% spoke English at home. We did not observe a significant improvement in the primary endpoint in evaluable patients – control (QuIC-A - 76.5/100) vs experimental arm (QuIC-A - 77.4/100), p value = 0.39 (one sided, two sample t-test). 20 participants provided feedback on the enhanced consent materials via a study questionnaire –75% found both the 2-page study aid and the videos not at all distressing or uncomfortable and 85% found them either quite useful or very useful. Conclusions: This is the first prospective randomized trial evaluating the impact of communication interventions on informed consent in advanced cancer patients considering early phase oncology clinical trials. The co-designed interventions were deliverable online and were acceptable and useful for patients. We did not demonstrate an improvement in the primary endpoint with a high QuIC-A score observed in the control arm- this could be explained by the study population which was highly educated, White and spoke English at home. Future studies should focus on groups with lower literacy and from culturally and linguistically diverse backgrounds. Clinical trial information: NCT04407676 .

Development of a risk-tailored approach and dashboard for efficient management and monitoring of investigator-initiated trials

BackgroundMost randomized controlled trials (RCTs) in the academic setting have limited resources for clinical trial management and monitoring. Inefficient conduct of trials was identified as an important source of waste even in well-designed studies. Thoroughly identifying trial-specific risks to enable focussing of monitoring and management efforts on these critical areas during trial conduct may allow for the timely initiation of corrective action and to improve the efficiency of trial conduct. We developed a risk-tailored approach with an initial risk assessment of an individual trial that informs the compilation of monitoring and management procedures in a trial dashboard.MethodsWe performed a literature review to identify risk indicators and trial monitoring approaches followed by a contextual analysis involving local, national and international stakeholders. Based on this work we developed a risk-tailored management approach with integrated monitoring for RCTs and including a visualizing trial dashboard. We piloted the approach and refined it in an iterative process based on feedback from stakeholders and performed formal user testing with investigators and staff of two clinical trials.ResultsThe developed risk assessment comprises four domains (patient safety and rights, overall trial management, intervention management, trial data). An accompanying manual provides rationales and detailed instructions for the risk assessment. We programmed two trial dashboards tailored to one medical and one surgical RCT to manage identified trial risks based on daily exports of accumulating trial data. We made the code for a generic dashboard available on GitHub that can be adapted to individual trials.ConclusionsThe presented trial management approach with integrated monitoring enables user-friendly, continuous checking of critical elements of trial conduct to support trial teams in the academic setting. Further work is needed in order to show effectiveness of the dashboard in terms of safe trial conduct and successful completion of clinical trials.