Transferring care to enhance access to early-phase cancer clinical trials: Protocol to evaluate a novel program.

Involving diverse populations in early-phase (phase I and II) cancer clinical trials is critical to informed therapeutic development. However, given the growing costs and complexities of early-phase trials, trial activation and enrollment barriers may be greatest for these studies at healthcare facilities that provide care to the most diverse patient groups, including those in historically underserved communities (e.g., safety-net healthcare systems). To promote diverse and equitable access to early-phase cancer clinical trials, we are implementing a novel program for the transfer of care to enhance access to early-phase cancer clinical trials. We will then perform a mixed-methods study to determine perceptions and impact of the program. Specifically, we will screen, recruit, and enroll diverse patients from an urban, integrated safety-net healthcare system to open and active early-phase clinical trials being conducted in a university-based cancer center. To evaluate this novel program, we will: (1) determine program impact and efficiency; and (2) determine stakeholder experience with and perceptions of the program. To achieve these goals, we will conduct preliminary cost analyses of the program. We will also conduct surveys and interviews with patients and caregivers to elucidate program impact, challenges, and areas for improvement. We hypothesize that broadening access to early-phase cancer trials conducted at experienced centers may improve equity and diversity. In turn, such efforts may enhance the efficiency and generalizability of cancer clinical research.

Exaggerated postural sway improves orthostatic cardiovascular and cerebrovascular control.

Introduction: Healthy individuals with poor cardiovascular control, but who do not experience syncope (fainting), adopt an innate strategy of increased leg movement in the form of postural sway that is thought to counter orthostatic (gravitational) stress on the cardiovascular system. However, the direct effect of sway on cardiovascular hemodynamics and cerebral perfusion is unknown. If sway produces meaningful cardiovascular responses, it could be exploited clinically to prevent an imminent faint. Methods: Twenty healthy adults were instrumented with cardiovascular (finger plethysmography, echocardiography, electrocardiogram) and cerebrovascular (transcranial Doppler) monitoring. Following supine rest, participants performed a baseline stand (BL) on a force platform, followed by three trials of exaggerated sway (anterior-posterior, AP; mediolateral, ML; square, SQ) in a randomized order. Results: All exaggerated postural sway conditions improved systolic arterial pressure (SAP, p = 0.001) responses, while blunting orthostatic reductions in stroke volume (SV, p < 0.01) and cerebral blood flow (CBFv, p < 0.05) compared to BL. Markers of sympathetic activation (power of low-frequency oscillations in SAP, p < 0.001) and maximum transvalvular flow velocity (p < 0.001) were reduced during exaggerated sway conditions. Responses were dose-dependent, with improvements in SAP (p < 0.001), SV (p < 0.001) and CBFv (p = 0.009) all positively correlated with total sway path length. Coherence between postural movements and SAP (p < 0.001), SV (p < 0.001) and CBFv (p = 0.003) also improved during exaggerated sway. Discussion: Exaggerated sway improves cardiovascular and cerebrovascular control and may supplement cardiovascular reflex responses to orthostatic stress. This movement provides a simple means to boost orthostatic cardiovascular control for individuals with syncope, or those with occupations that require prolonged motionless standing.

Enhancing access to and diversity in cancer clinical trials through a financial reimbursement program: Protocol to evaluate a novel program.

As clinical trials have become more complex, with increasing numbers of required procedures and clinic visits, gaining access to promising new treatments has become even more challenging for many individuals. To address these barriers, we implemented a financial reimbursement and outreach program designed to increase the number and diversity of participants in cancer clinical trials at centers in Dallas, Houston, and Philadelphia. As endorsed by U.S. Food and Drug Administration (FDA) and the Texas and Pennsylvania State Legislatures, the program provides financial reimbursement for non-clinical costs (e.g., travel, lodging) to patients on cancer clinical trials with household income up to 700% the Federal poverty rate. The research study described here, centered at the Dallas site, evaluates program impact by assessing (1) numbers and diversity of patients enrolled to cancer clinical trials before and after program implementation; (2) characteristics of patients offered participation in the program who do versus do not enroll; (3) characteristics of patients enrolled in the program who do versus do not complete the reimbursement process. To evaluate perceived barriers and facilitators of program participation, we will conduct semi-structured interviews and administer the Comprehensive Score for Financial Toxicity Patient Reported Outcome Measure (COST PROM) and the Short Assessment of Health Literacy (SAHL). This program will examine how reimbursement of non-clinical costs can improve access to cancer clinical trials, with the eventual goal of increasing trial enrollment, diversity, representativeness, and generalizability.

The effect of water temperature on orthostatic tolerance: a randomised crossover trial.

PURPOSE: Bolus water drinking, at room temperature, has been shown to improve orthostatic tolerance (OT), probably via sympathetic activation; however, it is not clear whether the temperature of the water bolus modifies the effect on OT or the cardiovascular responses to orthostatic stress. The aim of this study was to assess whether differing water temperature of the water bolus would alter time to presyncope and/or cardiovascular parameters during incremental orthostatic stress. METHODS: Fourteen participants underwent three head-up tilt (HUT) tests with graded lower body negative pressure (LBNP) continued until presyncope. Fifteen minutes prior to each HUT, participants drank a 500 mL bolus of water which was randomised, in single-blind crossover fashion, to either room temperature water (20 °C) (ROOM), ice-cold water (0-3 °C) (COLD) or warm water (45 °C) (WARM). Cardiovascular parameters were monitored continuously. RESULTS: There was no significant difference in OT in the COLD (33 ± 3 min; p = 0.3321) and WARM (32 ± 3 min; p = 0.6764) conditions in comparison to the ROOM condition (31 ± 3 min). During the HUT tests, heart rate and cardiac output were significantly reduced (p < 0.0073), with significantly increased systolic blood pressure, stroke volume, cerebral blood flow velocity and total peripheral resistance (p < 0.0054), in the COLD compared to ROOM conditions. CONCLUSIONS: In healthy controls, bolus cold water drinking results in favourable orthostatic cardiovascular responses during HUT/LBNP without significantly altering OT. Using a cold water bolus may result in additional benefits in patients with orthostatic intolerance above those conferred by bolus water at room temperature (by ameliorating orthostatic tachycardia and enhancing vascular resistance responses). Further research in patients with orthostatic intolerance is warranted.

Longitudinal Experience With and Impressions of COVID-19-Related Clinical Research Changes.

PURPOSE: The COVID-19 pandemic has led to profound changes in clinical research, including remote consent, telehealth, off-site procedures, shipment of therapy, and remote study monitoring. We assessed longitudinal perceptions of these adjustments among clinical research professionals. METHODS: We distributed an anonymous survey assessing experiences, perceptions, and recommendations regarding COVID-19-related clinical research adjustments to cancer clinical research office personnel in May 2020 and again in November 2020. Responses were compared using Fisher's exact and Mann-Whitney U tests. RESULTS: A total of 90 of 102 invited research personnel (88%) responded. Fifty-three (59%) reported participating in both initial and follow-up surveys. The proportion of respondents reporting personal experience with COVID-19-related adjustments increased over time, particularly for remote initial consent (29% v 4%), remote reconsent (24% v 9%), and remote study monitoring (36% v 22%). Perceived impact of COVID-19-related adjustments on data quality (P = .02) and patient experience (P = .002) improved significantly. However, perceived effect on patient safety (P = .02) and respondent's experience (P = .09) became less favorable. Individuals with personal experience with the adjustment were more likely to recommend continuing remote consent (62% v 38%; P = .04), remote monitoring (69% v 45%; P = .05), and therapy shipment (67% v 35%; P = .01) after the COVID-19 pandemic, with nonsignificant trends for off-site diagnostics (44% v 24%; P = .13) and telehealth visits (66% v 45%; P = .08). CONCLUSION: More than 6 months into the global pandemic, perceptions of COVID-19-related clinical research changes remain favorable. Experienced individuals are more likely to recommend that these changes continue in the future.

Application of Information Technology to Clinical Trial Evaluation and Enrollment: A Review.

IMPORTANCE: As cancer treatment has become more individualized, oncologic clinical trials have become more complex. Increasingly numerous and stringent eligibility criteria frequently include tumor molecular or genomic characteristics that may not be readily identified in medical records, rendering it difficult to best match clinical trials with clinical sites and to identify potentially eligible patients once a clinical trial has been selected and activated. Partly because of these factors, enrollment rates for cancer clinical trials remain low, creating delays and increased costs for drug development. Information technology (IT) platforms have been applied to the implementation and conduct of clinical trials to improve efficiencies in several medical fields, and these platforms have recently been introduced to oncologic studies. OBSERVATIONS: This review summarizes cancer and noncancer studies that used IT platforms for assistance with clinical trial site selection, patient recruitment, and patient screening. The review does not address the use of IT in other aspects of clinical research, such as wearable physical activity monitors or telehealth visits. A large number of IT platforms (which may be patient facing, site or investigator facing, or sponsor facing) are now commercially available. These applications use artificial intelligence and/or natural language processing to identify and summarize protocol eligibility criteria, institutional patient populations, and individual electronic health records. Although there is an expanding body of literature examining the role of this technology, relatively few studies to date have been performed in oncologic settings. CONCLUSIONS AND RELEVANCE: This review found that an increasing number and variety of IT platforms were available to assist in the planning and conduct of clinical trials. Because oncologic clinical care and clinical trial protocols are particularly complex, nuanced, and individualized, published experience with this technology in other fields may not be fully applicable to cancer settings. The extent to which these services will overcome ongoing and increasing challenges in cancer clinical research remains unclear.

Experience, Perceptions, and Recommendations Concerning COVID-19-Related Clinical Research Adjustments.

BACKGROUND: During the COVID-19 public health emergency, the FDA and NIH altered clinical trial requirements to protect participants and manage study conduct. Given their detailed knowledge of research protocols and regular contact with patients, clinicians, and sponsors, clinical research professionals offer important perspectives on these changes. METHODS: We developed and distributed an anonymous survey assessing COVID-19-related clinical trial adjustment experiences, perceptions, and recommendations to Clinical Research Office personnel at the Harold C. Simmons Comprehensive Cancer Center. Responses were compared using the Fisher exact test. RESULTS: A total of 94 of 109 contacted research personnel (87%) responded. Among these individuals, 58% had >5 years' professional experience in clinical research, and 56% had personal experience with a COVID-19-related change. Respondents perceived that these changes had a positive impact on patient safety; treatment efficacy; patient and staff experience; and communication with patients, investigators, and sponsors. More than 90% felt that positive changes should be continued after COVID-19. For remote consent, telehealth, therapy shipment, off-site diagnostics, and remote monitoring, individuals with personal experience with the specific change and individuals with >5 years' professional experience were numerically more likely to recommend continuing the adjustment, and these differences were significant for telehealth (P=.04) and therapy shipment (P=.02). CONCLUSIONS: Clinical research professionals perceive that COVID-19-related clinical trial adjustments positively impact multiple aspects of study conduct. Those with greatest experience-both specific to COVID-19-related changes and more generally-are more likely to recommend that these adjustments continue in the future.

Definition and Coordination of Roles and Responsibilities Among Cancer Center Clinic and Research Personnel.

PURPOSE: Effective enrollment and treatment of patients in cancer clinical trials require definition and coordination of roles and responsibilities among clinic and research personnel. MATERIALS AND METHODS: We developed a survey that incorporated modified components of the Survey of Physician Attitudes Regarding the Care of Cancer Survivors. Surveys were administered to clinic nursing staff and research personnel at a National Cancer Institute-designated comprehensive cancer center. Results were analyzed using χ2-tests, t tests, and analyses of variance. RESULTS: Surveys were completed by 105 staff members (n = 50 research staff, n = 55 clinic staff; 61% response rate). Research staff were more likely to feel that they had the skills to answer questions, convey information, and provide education for patients on trials (all P < .05). Both clinic and research staff reported receipt of communication about responsibilities in fewer than 30% of cases, although research staff reported provision of such information in more than 60% of cases. Among 20 tasks related to care of patients in trials, no single preferred model of responsibility assignment was selected by the majority of clinic staff for nine tasks (45%) or by research staff for three tasks (15%). Uncertainty about which team coordinates care was reported by three times as many clinic staff as research staff (P = .01). There was also substantial variation in the preferred model for delivery of care to patients in trials (P < .05). CONCLUSION: Knowledge, attitudes, and perception of care and responsibilities for patients on clinical trials differ between and among clinic and research personnel. Additional research about how these findings affect efficiency and quality of care on clinical trials is needed.

US Cancer Centers of Excellence Strategies for Increased Inclusion of Racial and Ethnic Minorities in Clinical Trials.

PURPOSE: Participation of racial and ethnic minority groups (REMGs) in cancer trials is disproportionately low despite a high prevalence of certain cancers in REMG populations. We aimed to identify notable practices used by leading US cancer centers that facilitate REMG participation in cancer trials. METHODS: The National Minority Quality Forum and Sustainable Healthy Communities Diverse Cancer Communities Working Group developed criteria by which to identify eligible US cancer centers-REMGs comprise 10% or more of the catchment area; a 10% to 50% yearly accrual rate of REMGs in cancer trials; and the presence of formal community outreach and diversity enrollment programs. Cancer center leaders were interviewed to ascertain notable practices that facilitate REMG accrual in clinical trials. RESULTS: Eight cancer centers that met the Communities Working Group criteria were invited to participate in in-depth interviews. Notable strategies for increased REMG accrual to cancer trials were reported across five broad themes: commitment and center leadership, investigator training and mentoring, community engagement, patient engagement, and operational practices. Specific notable practices included increased engagement of health care professionals, the presence of formal processes for obtaining REMG patient/caregiver input on research projects, and engagement of community groups to drive REMG participation. Centers also reported an increase in the allocation of resources to improving health disparities and increased dedication of research staff to REMG engagement. CONCLUSION: We have identified notable practices that facilitate increased participation of REMGs in cancer trials. Wide implementation of such strategies across cancer centers is essential to ensure that all populations benefit from advances in an era of increasingly personalized treatment of cancer.

Cancer Center Clinic and Research Team Perceptions of Identity and Interactions.

PURPOSE: Conduct of cancer clinical trials requires coordination and cooperation among research and clinic teams. Diffusion of and confusion about responsibility may occur if team members' perceptions of roles and objectives do not align. These factors are critical to the success of cancer centers but are poorly studied. METHODS: We developed a survey adapting components of the Adapted Team Climate Inventory, Measure of Team Identification, and Measure of In-Group Bias. Surveys were administered to research and clinic staff at a National Cancer Institute-designated comprehensive cancer center. Data were analyzed using descriptive statistics, t tests, and analyses of variance. RESULTS: Responses were received from 105 staff (clinic, n = 55; research, n = 50; 61% response rate). Compared with clinic staff, research staff identified more strongly with their own group ( P < .01) but less strongly with the overall cancer center ( P = .02). Both clinic staff and research staff viewed their own group's goals as clearer than those of the other group ( P < .01) and felt that members of their groups interacted and shared information within ( P < .01) and across ( P < .01) groups more than the other group did. Research staff perceived daily outcomes as more important than did clinic staff ( P = .05), specifically research-related outcomes ( P = .07). CONCLUSION: Although there are many similarities between clinic and research teams, we also identified key differences, including perceptions of goal clarity and sharing, understanding and alignment with cancer center goals, and importance of outcomes. Future studies should examine how variation in perceptions and group dynamics between clinic and research teams may impact function and processes of cancer care.

Resolving Rivalries and Realigning Goals: Challenges of Clinical and Research Multiteam Systems.

This article describes the care processes for a 64-year-old man with newly diagnosed advanced non-small-cell lung cancer who was enrolled in a first-line clinical trial of a new immunotherapy regimen. The case highlights the concept of multiteam systems in cancer clinical research and clinical care. Because clinical research represents a highly dynamic entity-with studies frequently opening, closing, and undergoing modifications-concerted efforts of multiple teams are needed to respond to these changes while continuing to provide consistent, high-level care and timely, accurate clinical data. The case illustrates typical challenges of multiteam care processes. Compared with clinical tasks that are routinely performed by single teams, multiple-team care greatly increases the demands for communication, collaboration, cohesion, and coordination among team members. As the case illustrates, the described research team and clinical team are separated, resulting in suboptimal function. Individual team members interact predominantly with members of their own team. A considerable number of team members lack regular interaction with anyone outside their team. Accompanying this separation, the teams enact rivalries that impede collaboration. The teams have misaligned goals and competing priorities that create competition. Collective identity and cohesion across the two teams are low. Research team and clinical team members have limited knowledge of the roles and work of individuals outside their team. Recommendations to increase trust and collaboration are provided. Clinical providers and researchers may incorporate these themes into development and evaluation of multiteam systems, multidisciplinary teams, and cross-functional teams within their own institutions.

The Automaticity of Social Life.

Much of social life is experienced through mental processes that are not intended and about which one is fairly oblivious. These processes are automatically triggered by features of the immediate social environment, such as the group memberships of other people, the qualities of their behavior, and features of social situations (e.g., norms, one's relative power). Recent research has shown these nonconscious influences to extend beyond the perception and interpretation of the social world to the actual guidance, over extended time periods, of one's important goal pursuits and social interactions.