Bedside manner or technical quality? Building advocacy for clinical trial participation via rapport

AIDS Clinical Trials Is There Access for All?

Encouraging participation in cancer clinical trials, one step at a time.

Purpose: Thirty years after the NIH Revitalization Act, racial/ethnic minority (REM) patients continue to be underrepresented in oncology clinical trials with disproportionately low rates of participation compared to non-Hispanic whites. Health system, patient, and medical provider factors contribute to this disparity. However, little is known about clinical trial investigator perspectives of REM participation in oncology clinical trials and their contribution to this disparity. To our knowledge there are no published quantitative studies that have investigated this important and actionable topic. Methods: We conducted a cross-sectional, anonymous, pilot survey of medical, radiation, and surgical oncology clinical trial investigators at a large academic center. Over a 5-week period, 107 individuals received a survey. The survey assessed 6 domains regarding disparities in REM participation in clinical trials: investigator knowledge, attitudes, and prior training on the topic, self-efficacy and motivation for improvement in addressing known disparities, and perceived barriers to REM participation in clinical trials. Modified, previously validated items were used when possible. Results: Of 60 respondents (56% response rate), 33 were male (55%). Thirty-six identified as non-Hispanic white (60%), 16 as Asian (27%), 1 as Hispanic/Latinx (2%), and 7 as other/prefer not to state (11%). Respondents included 49 medical (82%), 7 surgical (11%), and 4 radiation oncologists (7%). Average time as a clinical trial investigator was 14 years (2-40). Respondents opened an average of 2 clinical trials as primary investigator in the past year (0-10). A majority (83%) strongly agreed disparities exist in REM clinical trial participation and that the resulting lack of diversity is problematic (75%). However, only 34% strongly agreed they consider ways to achieve racial/ethnic diversity among trial participants when designing clinical trials, or ways to specifically enroll REM patients (28%). Respondents most commonly cited patient rather than health system factors as barriers to REM participation in clinical trials. Notably, nearly half (45%) agreed that lack of REM participation is a problem they cannot directly address. A majority (83%) endorsed wanting to improve their consideration of barriers to REM participation as they design clinical trials and wanted help to improve (86%). Conclusion: Our results suggest there is awareness among clinical trial investigators at our academic center of disparities in REM participation in oncology clinical trials and the problem this poses to cancer care. There is also a pervasive view that primary barriers to REM participation are patient factors, and investigators do not feel they can directly address these. Nonetheless, there is motivation among investigators to improve in their ability to consider barriers to REM participation as they design clinical trials. Interventions that improve investigators’ self-efficacy for addressing barriers to REM participation in clinical trials, especially patient level barriers, are needed. Citation Format: Natalie P. Bransky, Anne M. Walling, John A. Glaspy, Maria Garcia-Jimenez. Exploring the unexplored: Clinical trial investigator perspectives of disparities in racial/ethnic minority participation in oncology 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 A078.

Diversity and Inclusion in Pancreatic Cancer Clinical Trials

AIDS clinical trials. Is there access for all?

e23023 Background: Family caregivers are key stakeholders in cancer clinical trial decisions who have been overlooked in previous research. Caregivers play a critical role in supporting patients during clinical trial participation, yet there is little consensus regarding how they should be included in informed consent. Clinical trial staff communicate regularly with patients and caregivers during consent and throughout trial participation, making their perspectives vital to understanding the role caregivers play in these decisions. Methods: This qualitative study identifies the roles caregivers play in cancer trial decision-making, influential factors from the caregiver perspective, and practices of clinical trial staff regarding caregiver inclusion in consent. Patients who were offered a clinical trial at a midwestern comprehensive cancer center were asked to identify a caregiver to participate. Clinical trial staff were recruited via email invitation. We conducted focus groups with caregivers and trial staff, followed by semi-structured interviews with caregivers. Caregivers were asked about attitudes towards research, experiences with trial consent, and their role in decision-making. Trial staff were asked how they included caregivers in consent and attitudes towards their involvement. Transcripts were coded, then analyzed with NVivo using content analysis. Results: Focus groups consisted of 9 caregivers and 10 clinical trial staff, then 15 caregivers completed interviews. Caregiver themes included promoting patient autonomy, influential factors, and burdens of trial participation. Trial staff themes were approaches to caregiver inclusion, navigating challenging situations, and the need for training. Caregivers viewed their role as supporting patient understanding and deferring to the patient as final decision-maker. Hope for therapeutic benefit, oncologist endorsement, and practical barriers (e.g. cost, distance) were influential. Trial staff viewed caregivers as highly influential and encouraged their involvement in consent despite occasional challenges such as family disagreement and undue influence. Conclusions: Early communication with caregivers when offering a trial is vital due to their influential role in decision-making. Clinical trial staff would benefit from training on best practices for inclusion of caregivers, including communication, managing emotions, mediating disagreement, and where to refer caregivers for support. Researchers should consider caregiver burden and potential sources of caregiver support during trial design to minimize barriers to participation.

The Native Hawaiian population of Hawaii has disproportionately high cancer incidence and mortality rates. Native Hawaiian women with breast cancer present at an advanced stage and have death rates that are 52 % above the state average. Prostate cancer among Native Hawaiian men is diagnosed at more advanced stage. Native Hawaiian participation in cancer clinical trials was historically low. Reasons for this were varied including access, health literacy, lack of primary and referring physician awareness/time constraints and cultural barriers. Since the establishment of the University of Hawaii Minority Based Clinical Oncology Program (UHMBCCOP) participation in cancer clinical trials has definitely increased. MBCCOP provided clinical trial promotion, increased access and clinical trial support for a group of hospital and office based oncologists across the islands of Oahu and Kauai have all contributed to the increase. Education programs in Hawaii by multiple organizations, in particular, Imi Hale, the Native Hawaiian Cancer Network Program have enhanced knowledge of cancer and clinical trials in the Native Hawaiian community. Imi Hale's emphasis has focused on community based patient training, patient navigation and referring physician cancer clinical trial training. In fact, a recent program was recently initiated in conjunction with Education Network to Advance Clinical Trials (ENNACT) and Queens Medical Center. Review of Native Hawaiian participation in both cancer prevention and treatment trials through the UHMBCCOP over the last 20 years shows a significant gender difference with more women participating in both prevention and treatment trials. The reasons for this are not well understood but are under investigation. In summary, increased focused access and community based education have improved Native Hawaiian participation in cancer clinical trials but challenges persist including gender disparities in enrollment onto clinical trials and lack of access outside of Oahu and Kauai islands. Citation Format: Jeffrey L. Berenberg. Overcoming cultural and geographic barriers to participation in clinical trials among Native Hawaiians. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PL02-03. doi:10.1158/1538-7755.DISP13-PL02-03

Rethinking trial eligibility in the NCD era

ogists, radiation oncologists, and surgeons who were involved in the care of patients with colorectal or lung cancer. The investigators identified physician and infrastructure factors associated with clinical trial participation within the Cancer Care Outcomes Research and Surveillance Consortium, a partnership of academic and Veterans Administration hospitals with community outreach that are funded to do clinical research on cancer outcomes (2). Among the more telling findings: Physicians who saw a higher number of patients and who spent more time with each new patient had higher clinical trial accrual rates. Specifically, the majority of medical oncologists (59.4%) saw more than 20 colorectal or lung cancer patients per month, whereas the majority of surgeons (65%) saw fewer than five of these patients per month. The majority of medical oncologists (63.5%) and radiation oncologists (84%) spent 60 minutes or more with a new cancer patient visit, whereas the majority of surgeons (81.4%) spent less than 60 minutes. Factors that may facilitate discussion of treatment options with other physicians, such as teaching medical students or residents and attending tumor board meetings, were found to be associated with a higher likelihood of accruing or referring patients to trials. As expected, frequent participation in tumor board meetings (ie, weekly or monthly) was associated with higher rates of accrual, most likely because patients could be promptly referred to trials with specific eligibility requirements. However, participation in discussion formats is only a small part of the story, given that only 869 (56.7%) of physicians in the study had accrued or referred at least one patient to a clinical trial during the previous 12 months. Clinical trials require additional work beyond the usual practice of cancer care. Physicians who participate in clinical trials do not necessarily do so for their own financial gain, as supported by this study. Specific resources in the form of trained staff such as research nurses, staff to handle institutional review board issues, and investigational pharmacists and resources, such as physical space and information technology support, are essential to incorporate clinical trials into daily practice. Physicians who were affil iated with a National Cancer Institute–designated cancer centers (3) or a Community Clinical Oncology Program (4), two programs designed to provide that infrastructure, were associated with more accrual and referral. And yet, the research support is not sufficient: As Klabunde et al. (1) show in their secondary analysis, 34% of physicians affiliated with an organization designed to support clinical trial participation are not actively participating in the research. It appears that “the desire is present, but the body is unwilling.” What are the barriers to active participation by these physicians who have agreed (implicitly or explicitly) to participate? Are physicians inadequately trained for the additional responsibilities required of them to participate in clinical trials? Is it the additional work at a time when so many demands are made of them inhibiting their participation? What are reasonable expectations of physicians with regard to participation in clinical trials? The American public continues to value investment in medical research. In 2010, more than 70% of the general public were likely to consider participating in a clinical trial, but only 6% of their physicians offered that participation (5). A recent survey of patients seen at the Mayo Clinic showed that 76% of patients expected their treating physician to inform them about current trials (6). A more in-depth evaluation of the physician–patient encounter noted that of those patients who were offered participation in a cancer clinical trial, 75% agreed to participate, but only 20% of all of the patients (who were potentially eligible) were explicitly offered participation in a trial (7).

Background: Ensuring adequate, informed, and timely participation in clinical trials is a multifactorial problem. We have previously developed a systematic, tailorable survey development approach that is informed by theory, can identify barriers and enablers to participation, and can suggest recruitment strategies to address these issues. In this study, we surveyed subscribers to the Canadian Breast Cancer Network (CBCN) in order to identify a comprehensive list of theory-informed barriers and enablers relevant to participation in a hypothetical breast cancer trial. Methods: We developed and conducted an online survey of breast cancer patients informed by the Theoretical Domains Framework and designed to determine previous experience with clinical trials, knowledge about clinical trials, and importance of a comprehensive list of barriers and enablers to trial participation. Participants were contacted by email or through social media. Results: From 2451 subscribers of the CBCN, we received 244 responses and 210 completed surveys (244/2451 or 9.9% participation, 210/244 or 86.1% completion). A total of 38% of respondents indicated experience in trial participation, but 83% indicated confidence in their knowledge about clinical trials. Those who had previously participated in clinical trials were more confident in their knowledge (χ2= 6.77, p = 0.009) and answered more knowledge questions (t = −3.90 p = 0.000). Endorsed barriers and enablers to participation included 39 factors across 12 of 14 domains relevant to behaviour change. Our approach identifies barriers that might be meaningfully addressed by careful knowledge provision (‘If I would learn more about my condition’; ‘If I find the trial documents hard to understand’), those that may require other theory-informed approaches to address (‘my feelings about the quality of my drug plan’; ‘my worry over unknown side effects’), and those that may require tailored approaches depending on participant differences such as previous experience in trials (‘If there were patient-friendly decision-making tools to help you make your participation decision’). Discussion: This work demonstrates that a comprehensive, theory-guided survey of barriers and enablers to participation in breast cancer clinical trials is feasible, can lead to detailed knowledge about the issues related to participation in specific trials, and most importantly, can lead to insights about evidence-based ways to better support patient participation.

Mitigating Administrative Risks in Industry-sponsored Clinical Trials

108 Background: Thirty years after the NIH Revitalization Act, racial/ethnic minority (REM) patients remain underrepresented in oncology clinical trials. Little is known about clinical trial investigator perspectives of REM participation in clinical trials. To our knowledge no published studies exist assessing differences in investigator perspectives based on their primary role in the clinical trial process. We hypothesized that differences exist in investigator perspectives regarding REM participation in oncology clinical trials based on having a more design-oriented (principal (PI)/co-investigator (co-I)) or recruitment-oriented role (sub-investigator (sub-I)). Methods: We conducted a cross-sectional, anonymous, pilot survey of oncology clinical trial investigators at an academic center. Over 5 weeks, 107 individuals received a survey assessing 6 domains about disparities in REM participation in clinical trials, including knowledge, attitudes, and prior training. Modified, previously validated items were used if possible. We performed a subset analysis of mid- and late-career investigators (>/= 10 years of experience) comparing those who opened at least 1 clinical trial in the past year as PI or co-I to those who did not (sub-I). Results: There were 60 respondents (56% response rate). Average time as a clinical trialist was 14 years (2-40). Average number of trials opened in the last year as PI/co-I was 4 (1-30). Among all respondents, 83% strongly agreed disparities exist in REM clinical trial participation and that lack of diversity is problematic (75%). Notably, 45% agreed this is a problem they cannot directly address. Among mid- and late-career investigators, those who opened at least 1 trial as PI/co-I were more likely to have received training about barriers/facilitators (OR=3.56; 95% CI=1.05, 12.04; p=.04) to REM clinical trial participation and about strategies for improving participation (OR=3.75; 95% CI=1.06, 13.29; p=.04). Despite this, they were more likely to endorse wanting help to improve in this area (OR=4.95; 95% CI=1.17, 21.02; p=.03). Conclusions: Our results suggest there is awareness among clinical trial investigators of disparities in REM clinical trial participation, but investigators do not feel they can directly address these. Investigators who are more involved in clinical trial design are more likely to want help to improve their ability to address disparities in REM trial participation despite being more likely to have received prior training on the topic. Our findings suggest training alone is inadequate support for investigators involved in designing clinical trials. More studies eliciting the needs of investigators with varying roles in the clinical trial process are needed to inform targeted interventions to enhance investigators’ self-efficacy for improving REM participation in clinical trials.

Racial and ethnic disparities in breast cancer clinical trial participation pose a significant barrier to providing equitable care. Black and Hispanic patients are underrepresented in clinical trials, and an improved understanding of barriers to enrollment is needed. To examine patterns of clinical trial discussion and participation and patient attitudes toward clinical trial participation in a diverse cohort of patients with breast cancer. This cross-sectional study used survey data from patients enrolled in the Chicago Multiethnic Epidemiologic Breast Cancer Cohort. Patients were queried about clinical trial discussion and subsequent enrollment in a therapeutic clinical trial. Barriers to trial enrollment were also assessed. Surveys were conducted from July to September 2022, and data were analyzed from February to October 2024. Self-reported race and ethnicity, including Asian, Black, Hispanic, and White. Outcomes of interest were discussing participation in a breast cancer clinical trial with a health care practitioner, participating in a clinical trial, and barriers to trial enrollment. Of 1150 respondents (mean [SD] age, 53.7 [11.9] years), 51 (4.4%) were Asian, 224 (19.5%) were Black, 35 (3.1%) were Hispanic, and 838 (73.0%) were White. A total of 447 respondents (38.9%) reported discussing trial participation with a health care practitioner. There were no differences in trial discussion between White patients and other racial groups (Asian: adjusted odds ratio [AOR], 0.75; 95% CI, 0.31-1.82; Black: AOR, 1.31; 95% CI, 0.78-2.21; Hispanic: AOR, 0.73; 95% CI, 0.26-2.08). Among 443 patients offered a trial, 285 (64.3%) participated. While there were differences in trial participation across racial and ethnic groups, these differences were not significant after adjusting for sociodemographic and clinical factors. Among 158 patients who did not enroll in the trial offered, 37 (23.4%) reported ineligibility, 17 (10.8%) were worried about the possibility of getting a placebo, 16 (10.1%) were worried about extra time required, and 14 (8.9%) were worried about possible adverse effects. This cross-sectional study demonstrated that when offered, patients across racial and ethnic groups were equally likely to participate in clinical trials. In addition to ineligibility, time toxicity was a significant barrier to enrollment. These data provide valuable insights that can serve as a roadmap for how to expand access to trials for all patients, regardless of racial, ethnic, and socioeconomic background.

Introduction Randomized clinical trials (RCT) produce the highest level of evidence and therefore form the basis for many guidelines. Their Achilles heel is external validity which is still poorly studied. Participants in clinical trials may partly be selected on unknown mechanisms in particular regarding socioeconomic status. To what extent participants in clinical trials after myocardial infarction (MI) are representative for the overall MI population is unknown. Purpose To investigate whether participants in clinical trials after myocardial infarction differ regarding socioeconomic status (SES), risk factor profile, prior and recurrent cardiovascular disease (CVD) events. Methods A total of 34,084 patients attending follow up after myocardial infarction between 2007 and 2014 were identified in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) out of which 3,037 had participated in a clinical trial. Information on disposable income, education level, marital status, prior CVD, risk factors and treatment were retrieved from national registers and patients were followed regarding recurrent CVD. Participants in clinical trials were compared to non-participants using logistic and Cox regression analyses. In a multivariable Cox-regression analysis adjustments were made for gender, age, inclusion-year, diabetes, LVEF, previous MI, previous stroke, prior cardiac surgery, ECG rhythm, eGFR, lipid levels, smoking status, use of ASA, use of ACE-I, use of beta-blockers, use of statins, level of education, disposable income and family status. Results Trial participants were more likely to be men (odds ratio (OR): 1.42; 95% CI: 1.29–1.55)), to be married (1.17; 1.09–1.27), to have a high income (1.58; 1.45–1.72), have a post-secondary education (>12 years) (1.33; 1.22–1.46) and less likely to be smokers (0.81; 0.72–0.90), have a reduced EF <30% (0.61; 0.46–0.80), history of previous stroke (0.79; 0.65–0.97) or MI (0.86; 0.77–0.97) compared to non-participants. The risk for recurrent CVD was lower among the participants compared to the non-participants (HR: 0.77; 95% CI: 0.67–0.88) and is illustrated in figure 1. In a fully adjusted model the lower risk remained after adjusting for age, gender, risk factors, prior disease including EF, evidence based treatments and SES (HR: 0.85; 95% CI: 0.74–0.97). Trial participation and recurrent CVD Conclusion Participants in clinical trials after MI constitute a highly selected group with higher SES, a more favourable risk profile and a better overall prognosis. The lower risk after full adjustments imply that additional selection bias exists. The external validity of post MI- trials in general can thus be questioned. To what extent results from clinical trials apply to the overall post MI population should be carefully scrutinized. Real world registry data are important. Acknowledgement/Funding Familjen Janne Elgqvists Stiftelse

What is known and objectiveThe discussion about health equity in the United States frequently involves concerns over racial and ethnic minority under‐representation in clinical trials and particularly in trials conducted in support of product approvals. The FDA has long worked to encourage diverse participation in clinical trials and through its Drug Trials Snapshots (DTS) program, the U.S. Food and Drug Administration (FDA) has moved to make trial demographic data more accessible and transparent. We conducted a demographic study of U.S. participants in clinical trials for FDA‐approved new drugs (new molecular entities [NMEs], and original Biologics License Applications [BLAs]) from 2015 to 2019, as reported in DTS database with a purpose of understanding the extent to which U.S.‐based trials used to support product approvals represent the racial and ethnic diversity of the U.S. population by therapeutic area.MethodsParticipant‐level trial data were collected by accessing the FDA electronic common technical document (eCTD), for the applications used to publish each Snapshot. The therapeutic area (TA) for each drug was determined by review division assignment. The demographic data were analysed and compared to U.S. census data.Results and discussionWe examined 102,596 U.S. participants in trials of new drugs that were approved and presented in Drug Trials Snapshots between 2015 and 2019. White participation ranged from 51% in psychiatric trials to 90% in cardiovascular (CV) trials; Black or African American participation ranged from 5% in medical imaging to 45% in psychiatric trials; Asian participation ranged from 0.75% in CV to 4% in dermatologic trials; and Hispanic or Latino participation ranged from 1% in medical imaging to 22% in infectious diseases and gastroenterology trials.What is new and conclusionOur data showed variable representation of racial and ethnic minorities across therapeutic areas at the U.S. sites. Blacks or African Americans were represented at or above U.S. census estimates across most therapeutic areas, while Asians and American Indian or Alaska Natives were consistently underrepresented. Hispanic or Latino participation across most therapeutic areas was below U.S. census estimates, however, more variable, and a sizable proportion of data was missing. The next step is a comparison of trial participation based on disease prevalence and epidemiology, which is a more accurate assessment of trial diversity.