Abstract A43: Barriers, strategies, and recommendations to engaging African American women in clinical research: The recruiter's perspective

Cardiovascular disease (CVD) is the most common cause of death in American women and accounts for a full one-third of all deaths.1 Although the common perception may be that CVD affects mainly men, there is equal prevalence of this disease between the genders by the age of 40, and by the age of 60 more women than men are affected. More women than men have died from CVD causes on a yearly basis since the mid 1980s, and whereas the CVD mortality has steadily declined in men over the past 30 years, it has remained steady in women until very recently when CVD mortality was noted to decrease for both genders.2 See accompanying article on page 277 The impact of cardiovascular disease (CVD) on the health status of American women is gaining more recognition and has become the focus of public education efforts such as the “Go Red for Women” campaign sponsored by the American Heart Association and the “Red Dress” project sponsored by the Department of Health and Human Services, the National Institutes of Health (NIH), and the National Heart Lung and Blood Institute (NHLBI). These programs are, in part, a response to the increasing awareness of cardiovascular disease as a major source of morbidity and mortality in U.S. women. The importance of CVD as a major source of mortality in women was recognized early on by federally funded institutes including the Public Health Service Task Force, which brought attention to concerns about the health information available to women and the historical lack of research focus on women’s health in its 1985 Report of the Public Health Service Task Force on Women’s Health Issues .3 In response to this report, the National Institutes of Health adopted a policy for the inclusion of women in clinical research …

IA19: Elucidating the origins of aggressive breast cancer in African American women

IA42: Risk factors and ovarian cancer in African American women: Contributors to disparities

The participation of underserved ethnic minorities in clinical research is critical to achieving progress in cancer control. Ethnic minority patient accrual in clinical trials is a formidable challenge that requires patient trust, commitment, and overcoming of barriers. Racial and ethnic minorities make up about 40% of the United States population, yet are not well represented in research studies. Less than 10% of all patients with cancer enrolled in clinical trials are minorities. Diverse participation may lead to more generalizable results for under-represented groups, more best practices for prevention and treatment to specific minority groups, increase in knowledge and awareness of disparities about cancer, and a more accurate reflection of the United States' increasingly diverse population. Although there is a proliferation of patient navigation programs to increase health care among the underserved, there is little known on its potential effects as a strategy to enhance minority clinical trial and biospecimen accrual. City of Hope has built a functional and sustainable program for addressing health inequity, which includes training a network of community research navigators (CRN) to address gaps in knowledge, medical mistrust, and access, and navigate participation and engagement of under-represented groups in research. The research navigator program draws from the patient navigation and promotora model and is a novel and innovative application to this approach. This approach has utility and applicability to address research participation barriers, including trust and referrals. It promises sustainability and cost effectiveness as trained CRNs can deliver the program. The Community Research Navigator (CRN) project enhances community advocates' capacity by training community health leaders/promotoras as community research navigators (CRN) to widen the dissemination of the clinical trial and research participation enrollment for increased ethnic minority participation in clinical trials and health-related research. CRNs attended a 1-day training on clinical trials and research. The training included educating and encouraging individuals to proactively think about and discuss clinical trial participation with their family, friends, and health care providers; disseminating information about specific research studies, targeting the African and Latino communities; and referring individuals to specific biospecimen, clinical trials, and population studies. In total, we trained and mentored a team of 14 CRNs. Participants were 24-66 years old; most were female (86%), Latino (69%), and single (43%). After participating in the training, participants were more likely to correctly define HIPAA (p=.040) and the types of clinical trials (p=.038). In addition, CRNs were more likely to encourage clinical research participation among their family after the training (p=0.034). Further, we measured confidence in various domains, including: increase in confidence in describing the purpose and process of clinical research (p=0.006); educating minority communities about clinical trials (p=0.045); and providing informational workshops/forums on clinical research (p=0.046). Participants had an increase in overall confidence (p=.033). Our findings demonstrate that the CRN strategy holds promise in increasing minority participation in cancer clinical trials. It is an innovative application of the extensively studied patient navigation approach that warrants research. Future research should focus on the CRN project as a cost-effective tool for enrollment and retention of ethnic minorities in cancer clinical trials and the potential of enhancing clinical trial understanding outcomes among participants. Citation Format: Marisela Garcia, Mayra Serrano, Alejandro Fernandez, Katty Nerio, Kimlin Ashing. Community research navigators: The bridge to increasing ethnic minority participation in clinical research [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A25.

BackgroundThere is ambiguity with regard to what counts as an acceptable level of risk in clinical research in pregnant women and there is no input from stakeholders relative to such research risks. The aim of our paper was to explore what stakeholders who are actively involved in the conduct of clinical research in pregnant women deem an acceptable level of risk for pregnant women in clinical research. Accordingly, we used the APOSTEL VI study, a low-risk obstetrical randomised controlled trial, as a case-study.MethodsWe conducted a prospective qualitative study using 35 in-depth semi-structured interviews and one focus group. We interviewed healthcare professionals, Research Ethics Committee members (RECs) and regulators who are actively involved in the conduct of clinical research in pregnant women, in addition to pregnant women recruited for the APOSTEL VI case-study in the Netherlands.ResultsThree themes characterise the way stakeholders view risks in clinical research in pregnant women in general. Additionally, one theme characterises the way healthcare professionals and pregnant women view risks with respect to the case-study specifically. First, ideas on what constitutes an acceptable level of risk in general ranged from a preference for zero risk for the foetus up to minimal risk. Second, the desirability of clinical research in pregnant women in general was questioned altogether. Third, stakeholders proposed to establish an upper limit of risk in potentially beneficial clinical research in pregnant women in order to protect the foetus and the pregnant woman from harm. Fourth and finally, the case-study illustrates that healthcare professionals’ individual perception of risk may influence recruitment.ConclusionsHealthcare professionals, RECs, regulators and pregnant women are all risk adverse in practice, possibly explaining the continuing underrepresentation of pregnant women in clinical research. Determining the acceptable levels of risk on a universal level alone is insufficient, because the individual perception of risk also influences behaviour towards pregnant women in clinical research. Therefore, bioethicists and researchers might be interested in changing the perception of risk, which could be achieved by education and awareness about the actual benefits and harms of inclusion and exclusion of pregnant women.

The total value to society of eliminating all life expectancy disparities attributable to the underrepresentation of minorities for the three common conditions of diabetes, heart disease, and hypertension was approximately $11 trillion based on a commissioned analysis that applied the Future Elderly Model for the National Academies of Sciences, Engineering, and Medicine (NASEM) Committee on Improving the Representation of Women and Underrepresented Minorities in Clinical Trials and Research.1 While older adults experience higher rates of these comorbidities2 and polypharmacy3 than the general population and are the major utilizers of medications,4 they are considerably underrepresented in clinical trials and clinical research overall.5 The prioritization of COVID-19 vaccines for older adults as part of phase 1 by the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices was a prominent example of the importance of studying older adults and, particularly, older adults with chronic disease in clinical trials.6 To address the societally pressing challenge of the lack of older adults, women, and minorities in clinical trials and medical research in general, NASEM hosted a virtual workshop titled "Drug Research and Development for Adults Across the Older Age Span" in 2020. The following year through 2022, NASEM performed a Congressionally mandated consensus study with culminating report titled "Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups." The goal of these NASEM activities was to examine and shed light on the challenges and opportunities in drug research and development for older adults, women, and underrepresented groups and explore hurdles that impair clinical studies in these populations. The NASEM events described the array of consequences due to the underrepresentation of women and minoritized populations as well as the salient conclusions based on the evidence (Table 1). 1. Lack of representation compromises generalizability and relevance of clinical research findings to the whole U.S. population. 2. Lack of representation translates to hundreds of billions of dollars in medical costs in the United States. 3. Lack of representation may hinder innovation and new discoveries. 4. Lack of representation may compound low accrual that causes many trials to fail. 5. Lack of representation may lead to a lack of access to effective medical interventions. 6. Lack of representation may undermine the trust of the clinical research enterprise and the medical establishment. 7. Lack of representation may lead to the absence of determination and measurement of outcomes meaningful to these populations. 8. Lack of representation precludes ascertaining important variations in medication absorption and metabolism, which may be altered by age, sex/gender, and race/ethnicity. 1. Improving representation in clinical research is urgent. 2. Improving representation in clinical research requires substantial investment that must include education and dialogue with patients and communities who may be unfamiliar with clinical trials and may have concerns about potential risks as well as benefits. 3. Improving representation requires transparency and accountability. 4. Improving representation in clinical research is the responsibility of everyone involved in the clinical research enterprise. 5. Creating a more equitable future entails a paradigm shift. Barriers to the necessary representation of underrepresented and excluded populations in clinical research in the current research system have reduced participation by a diverse population in clinical trials and clinical research at multiple levels. Individual research studies, the institutions that conduct research, funders of studies, institutional review boards (IRBs), medical journals, and the broader landscape of national policies and practices that govern research all contribute to barriers of populations historically excluded from clinical research. At the level of an individual research study, the factors and problems that lead to the underrepresentation and exclusion of certain populations in clinical trials and research begin with and follow the life cycle of a project. Understanding and resolving the underrepresentation and exclusion of these populations in research require careful examination of almost every stage in the research process itself. This includes at the time research questions are developed. The composition, training, and attitudes of the research team must also be considered to foster the thoughtful dialogue and insight necessary to maximize representation of needed populations. Research site selection is also a key facet in bolstering access to priority populations for increasing representativeness. Intentionality in "meeting people where they are" has been identified as a key pillar in improving the representativeness and validity of studies. Consideration on participant selection and study protocols in general that includes determination of sampling approaches, recruitment methods, inclusion, and exclusion criteria must also be carefully evaluated. Appropriately performed this includes review of informed consent processes, remuneration for study participants, as well as development and inclusion of multilingual recruitment and consent documents. For older adults, it has been noted that while most older adults with the most common chronic conditions that result in hospitalization in the United States occur in older people with multiple conditions, having multiple conditions was often an exclusion criterion in the National Institutes of Health (NIH) trials. This approach effectively ensured that the representative older population was systematically excluded from the studies. Deliberate considerations of the consequences of inclusion and exclusion criteria decisions on representativeness must be prioritized as fundamental to the research. Institutional structures are also a barrier to appropriate inclusivity. Medical institutions of different types face a range of structural barriers to inclusion in clinical trials. For example, although academic medical centers conduct 55% of the extramural medical research supported by the NIH and operate 98% of the nation's 41 comprehensive cancer centers as of 2019, sustainably and meaningfully engaging underrepresented and excluded populations often does not align with the traditional incentive structures for researchers at these institutions. Recruiting diverse population groups and properly engaging with community members, which is time-consuming and requires investments to build and sustain trust, are only minimally considered in promotion and tenure decisions at academic medical centers. While community health centers serve a much more diverse community than academic medical centers, these institutions also face barriers to clinical trials and research recruitment, which include limited provider knowledge about available research opportunities and challenges with electronic health record (EHR) infrastructure, that can limit providers' ability to query the EHR using study inclusion and exclusion criteria. IRBs can also present barriers to diverse participation in clinical trials by limiting the types and amount of compensation given to research participants to avoid the impression of coercion or undue influence. However, limiting incentives may ultimately compromise beneficence and justice, two of the ethical principles for research with human subjects detailed in the Belmont Report.7 Research funders also have several roles and responsibilities, which can influence the diversity of clinical trials. These include setting funding priorities, deciding which projects ultimately get funded, providing adequate funding to recruit and retain participants, requiring transparent reporting, and evaluating research outputs. Most clinical trials are funded by pharmaceutical firms. These trials present barriers, including out-of-pocket costs for participants, which are often not discussed in the informed consent process, industry pressures to gather data quickly, and the selection of easy-to-recruit samples often being incentivized. It should be noted that some of these barriers are not solely unique to industry-sponsored trials. Peer-reviewed medical journals serve as the gatekeepers to scientific advancements in clinical practice and health. Their editors wield great power for what is, and is not, published in their pages. Lack of representation on editorial boards and other journal leadership positions may contribute to biases in publication. Recent focused efforts have been formalized to improve representation on journal editorial boards. This included the release of The Journal of the American Medical Association priorities to strive for and promote diversity, equity, and inclusion (DEI) that included the following key approaches: update journal mission statements to include inclusivity aims, appoint an editorial director of equity, improve editorial diversity, promote awareness of and responsibility for DEI, formalize process for assessment and reporting, expand editorial fellowship program, hold seminars on excellence in scientific writing, continue to publish articles on DEI, identify and invite peer reviewers and authors of opinion articles with DEI expertise, encourage authors to address systemic and structural problems to advance DEI, review and update inclusive language guidance for authors and editors update statistical analysis guidance, and participate in International Collaboration on Standards and Policies.8 While the JAMA effort is a necessary step, many more journals must plan, execute, and monitor their efforts to ensure representativeness regarding inclusivity. These activities from NASEM developed an array of policy considerations and recommendations to narrow the inclusiveness gap for minorities, women, and older adults in clinical research. In terms of bolstering reporting, transparency, and accountability, the NASEM report recommended that The Department of Health and Human Services (HHS) create a research equity task force within HHS charged with coordinating data collection and designing study subject recruitment and accrual monitoring that would track across federal agencies, including the Food and Drug Administration (FDA), NIH, CDC, Agency for Healthcare Research and Quality (AHRQ), Health Resources Services Administration (HRSA), Indian Health Services (IHS), and the Centers for Medicare & Medicaid Services (CMS). This task force would submit an annual report to Congress on the status of clinical trial and clinical research enrollment in the United States, which would include patient counts recruited into clinical studies by phase and condition. Mandated data would include the study patients' age, sex, gender, race, ethnicity, study location, and recruitment site. The annual report would also describe to what degree the study population was representative of the conditions studied as well as the sponsors of the research. Creating a real-time, data dashboard was offered as an example of a tool to make data more accessible and transparent continuously. The report also recommended clarifying how "representativeness" was determined and evaluated for protocols and product development plans.1 This would serve to not only help discern the older adult representation but allow for stratification of the older adult categories by minority, gender, and location to ensure that studies line up with actual disease prevalence for older adult subpopulations. This was coordinated with a frequent comment that the heterogeneity of older adults must be better tracked with improved tools and technology to enhance knowledge and treatment outcomes to increase the proportion of heterogeneous older adults in clinical trials. The improved use of modern tools was also broached in terms of better use of technology such as social media to improve recruitment of older adults from diverse backgrounds into trials.9 For a path toward equitable compensation to research participants and their caregivers, the NASEM report recommended developing specific guidance that would include systematically modified compensation for those who will experience a financial burden when participating in research activities. Receipt of a detailed recruitment plan should be required by the FDA no later than at the time of Investigational New Drug and Investigational Device Exemption application submission. To facilitate that trial characteristics are consistently labeled throughout the database and can be easily disaggregated, exported, and analyzed by the public, NIH should standardize the submission of demographic characteristics to ClinicalTrials.gov beyond current guidelines. A theme across the NASEM activities was that NIH can better leverage its role as a funder to motivate improved inclusiveness of older adults and minorities. The score-driving criteria that measure the scientific integrity and overall impact of a NIH grant proposal should formally include participant representativeness data. Patient representativeness data should be components of the assessment of the scientific approach, including whether it is appropriate for concluding insights for the populations to whom the results are intended to generalize. In the 2020 NASEM workshop, Alzheimer's disease research was referenced as an area in which representation of older adults would be expected. The concept of requiring a justification for not including older adults was described on several occasions.9 The NIH should also assess in its annual review of progress reports of funded studies whether a given study has met the proposed enrollment goals of representativeness by race/ethnicity, sex, and gender and should establish a plan for remediation that includes criteria for pausing funding that has not met predefined recruitment goals. Journal publisher, editors, and the International Committee on Medical Journal Editors should (1) require information on the representativeness of studies for submissions to their journals in context to the affected population; (2) consider this information in acceptance decisions; and (3) publish this information for manuscripts that are accepted. The overall representativeness of the trial, including how well the study population aligns with the target population, should be evident in the publication. The Office of Human Research Protections (OHRP) and the FDA should advise local IRBs determine and report the representativeness of clinical trials as one measure of sound research design. Study protocols in which the pre-specified enrollment departs markedly from the disease prevalence would trigger a request for a justification statement or possible remediation. The commitment to and value of educating review bodies across the clinical development continuum to incorporate considerations of age, gender, and minority status dimensions was a prevailing theme. In terms of coverage and payment, CMS should revise its guidance for coverage with evidence development to require that study protocols include a plan for recruiting and retaining participants who are representative of the affected beneficiary population in age, race, ethnicity, sex, and gender. Congress should direct the FDA to enforce accountability measures already present, as well as establish a taskforce to study new incentives for new drug applications for trials that achieve representative enrollment. This recommendation has in fact been enacted in the Food and Drug Omnibus Reform Act of 2022 (FDORA)10 that requires sponsors of phase 3 or other pivotal medication studies to submit diversity action plans by the time the study protocol is submitted. A synthesis of the current environment was recently detailed in the special article "Current status of inclusion of older groups in evaluations of new medications: Gaps and implementation needs to fill them" in this journal.11 Incentive programs should be designed to improve representativeness in clinical research and ensure they do not impede access to new therapies. Expedited coverage decisions should be considered for therapies based on clinical programs that achieve representativeness of the populations most affected. To incentivize community providers to enroll participants in trials, CMS should develop reimbursement approaches for the time and infrastructure that is required. Development of new payment codes would allow CMS to reimburse activities associated with clinical trial participation including data collection and personnel to support research education and recruitment endeavors. The Government Accountability Office (GAO) should assess the impact of previously enacted policies reimbursing routine care costs associated with CMS trials. To foster equitable compensation to research participants and their caregivers, federal agencies, including the OHRP, NIH, and FDA, should develop guidance to direct IRBs on appropriate remuneration for study participation. This new guidance should encourage and allow for variable compensation to research participants and their caregivers commensurate with the time commitment and financial burden of participating. There are trial designs tested that offer the prospect of increasing enrollment of older adults, including adaptive platform trial designs, home-based trials, mechanistic modeling, simulations, real-world data, and pragmatic clinical trials. Clinical trials can now be successfully completed in many non-traditional clinical trial environments that have included barber shops and pharmacies.9 Similarly, all sponsors of clinical trials and clinical research (e.g., federal, foundation, private, and/or industry) should ensure that trials provide adequate compensation for research participants. A diverse, inclusive, and representative workforce, particularly in leadership circles, should be maintained for all organizations involved in clinical research. Recognition of research, training, and professional activities to promote community-engaged scholarly efforts and other research to enhance clinical trial representativeness should be included as areas of excellence for promotion or tenure considerations. The HHS should substantially invest in research infrastructure in the community. To bolster the capacity of community health centers and safety net hospitals to participate in clinical research, funding should be directed to agencies such as the HRSA, NIH, AHRQ, CDC, and IHS. These recommendations and recent advances to date in each area are summarized in Table 2. Progress has been made at the government level with the passage of FDORA as well as coordinated efforts to improve representativeness in clinical research by other agencies, academic institutions, foundations, and non-governmental organizations. Yet, recommendations on changing the composition of the workforce and individual academic entities will require a longer timeframe and concerted effort as will building trust across all communities. Bridging the inclusion gaps for older adults, minorities, and women in clinical research is achievable and necessary. However, it will demand intentional and committed policy efforts with coordination from an array of stakeholders. Fortunately, informed guidance now exists that we must immediately harness and apply to reverse our flagging population health outcomes and move us closer to peer nations. Dr. Jonathan H. Watanabe contributed to the concept, design, and preparation of the manuscript. Dr. Jonathan H. Watanabe credits his involvement as a Member of the Forum on Drug Discovery, Development, and Translation of the National Academies of Sciences, Engineering, and Medicine (NASEM), a planning committee member for the Drug Research and Development for Older Adults Across the Older Age Span NASEM Workshop, and a prior National Academy of Medicine Emerging Leader in Health and Medicine Scholar. He would like to thank Dr. Janice Schwartz for her insightful feedback that strengthened this manuscript. The information or contents are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by NASEM or NAM. Jonathan H. Watanabe has received research funding from the National Institutes of Health and the National Academies of Sciences, Engineering, and Medicine. These organizations played no role in the design, development, writing, or review of this manuscript. None. None.

Background: Although European American (EA) women have higher incidence of breast cancer than African American (AA) women, AA women are more often diagnosed with aggressive estrogen receptor negative (ER-) tumors, the risk of which increases with parity, lack of breastfeeding, and an early age at menarche. DNA methylation could be affected by reproductive factors and may be a potential molecular mechanism driving differences in tumor etiology. In a small study using fresh frozen breast tissue (n=58 AA, 80 EA), we previously found more differentially methylated loci (DMLs) in ER- tumors from AA and EA women than in ER+ tumors. Methods: To follow up on these preliminary findings, we used the Illumina 450K platform to determine genome-wide DNA methylation profiles in formalin fixed paraffin embedded (FFPE) breast tumors from 383 AA and 350 EA women who participated in the Women's Circle of Health Study, a case control study conducted in NY and NJ. We identified DMLs by race and ER status, as well as differentially methylated regions (DMRs). DMLs in eight genes were validated using the Sequenom EpiTYPER platform. Recursively partitioned mixture modeling (RPMM) package in R was used to examine relationships between methylation clusters and reproductive factors, information available from in-person interviews. In addition, using fresh frozen tumor tissue from 50 patients treated at Roswell Park Cancer Institute, we performed RNA sequencing on samples with methylation data available from a prior study, and used Spearmen's correlation to compare methylation and gene expression of DMLs and DMRs. Results: In assessing average methylation by location relative to CpG-islands (CGIs), we found that CGIs and shores in ER- tumors were significantly hypomethylated compared to CGI and shores in ER+ tumors from AA women, but not in tumors from EA women. We also identified 410 DMLs (Δβ>0.10 & FDR<0.05) between AA and EA breast tumors (race-associated DMLs, raDMLs), the majority of which were unique to ER- tumors (n = 260) and hypomethylated in AAs. These loci were enriched for immune response genes and several cell adhesion and inflammatory pathways. RPMM showed that parity, but not breastfeeding or age at menarche, was significantly associated with methylation class of ER- breast tumors. Of the genes that had ER- specific raDMLs, FOXA1 and THSD4 DNA methylation was highly correlated with gene expression (rho=-0.80, rho=+0.87, respectively; pvalue< 2.2x10-16). Summary: ER- tumors from AA women, but not from EA women, exhibited global hypomethylation at CGI and shores compared to ER+ tumors and contained the majority of raDMLs, many of which were associated with genes involved in immune and inflammatory response. The FOXA1 gene, which encodes a pioneer factor previously implicated in suppressing the molecular phenotype of basal breast cancer cells, was found to be methylated and silenced in the majority of ER- tumors analyzed for expression, consistent with aggressiveness of these tumors. These results, and the novel finding of associations between parity and DNA methylation signature, bring us a step forward in understanding the heterogeneous population of ER- tumors and provide insight into mechanisms of racial disparities in breast cancer. Citation Format: Allyson C. Espinal, Dan Wang, Lara Sucheston-Campbell, Song Liu, Qiang Hu, Li Tang, Gary Zirpoli, Thaer Khoury, Song Yao, Kitaw Demissie, Elisa V. Bandera, Christine B. Ambrosone, Michael J. Higgins. Methylation differences in breast tumor DNA from African American and European women are predominant in estrogen receptor (ER) negative breast cancer and are associated with childbearing. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B47.

The persistence of health care disparities for disadvantaged populations in the United States is undisputed; elimination of these disparities is a high priority.1 A landmark report from a Task Force of the Secretary of Health and Human Services documented higher mortality and burden of disease in minorities.2 These data, as well as growing recognition of underrepresentation of women subjects in clinical research, prompted the NIH in 1986 to encourage the inclusion of women and minorities in clinical research. In 1993, the National Center for Minority Health and Health Disparities was established, recently redesignated as an Institute; Congress passed the NIH Revitalization Act, and the NIH subsequently implemented a revised policy that ensured inclusion of women and minorities in NIH-funded clinical research, specifying that their inclusion in phase III clinical trials be adequate in size to determine if gender or race/ethnicity subgroups had differential responses to the treatment being tested. NIH has since monitored these policies' effectiveness. In 2000, a new requirement for phase III clinical trials was the inclusion of a plan to conduct these subgroup or “valid” analyses by gender and by race/ethnicity, or a justification—exclusive of cost—as to why not, which must pass muster in peer review. Guidance for implementation of these requirements was formalized.3 Enrollment by gender and by race/ethnicity in National Institute of Neurological Disorders and …

Improving African American women's engagement in clinical research: A systematic review of barriers to participation in clinical trials

The NIH Precision Medicine Initiative (PMI) is being designed to improve health care and outcomes through the delivery of individualized patient care. A long-term goal for PMI is to develop a new model for conducting research that engages participants, shares data responsibly, and ensures privacy. As a result of having a greater understanding of the complex ways in which biological, social, behavioral, and clinical factors interact in diverse populations, the PMI is also expected to lead to the development of individualized prevention and treatment strategies that reduce racial disparities in morbidity and mortality. To achieve this, it is essential that racial and ethnic minorities be included in PMI cohorts and research activities. However, the challenges associated with recruiting and retaining minorities in clinical research are well-documented; reduced access to and knowledge about clinical trials and other types of research are among the key barriers to minority participation. The NCI Community Oncology Research Program (NCORP) was designed to address barriers to minority participation in cancer clinical trials and cancer care delivery research through infrastructure that supports the identification, enrollment, and retention of ethnic and racial minority cancer patients being treated in academic and community oncology settings. Infrastructure that supports the recruitment and retention of racial and ethnic minorities is necessary, but may not be sufficient to facilitate the enrollment of diverse populations in precision medicine research that is conducted through the NCORP. This is because precision medicine research may not be optimally described and designed to enhance informed decisions about enrollment. As PMI research is being developed, it is critical to be able to anticipate the rates at which individuals from diverse populations are likely to participate in studies. Recently, we demonstrated that African Americans are likely to consider potential benefits to themselves, family members, and their community as part of making a decision to participate in cancer genetics research. Yet, only 23% of African American respondents in a national sample of adults reported that it was very likely that they would donate personal health information and blood and/or tissue samples to a biobank. Concerns about exploitation, investigators' motives, and distrust of researchers were identified as being important to decisions about participating in cancer genetics research; distrust of researchers was associated with a significantly reduced likelihood of donating to a biobank. In addition, respondents who had greater positive expectations about participating in cancer genetics research and those who reported more participation facilitators relative to barriers were most likely to be willing to donate to a biobank. Even with positive expectations about study participation, the majority of African Americans may be unwilling to participate in research that: (1) was sponsored by the government to provide information about the health of African Americans, (2) participation involves answering a questionnaire and providing a cheek swab, (3) the data will be used for the current study and also may be shared with other researchers to conduct future studies, (4) participants would not receive any results. Overall, 31% of respondents reported that it was very or somewhat likely that they would participate in this type of study and 69% reported that it was very/somewhat unlikely or neutral that they would participate in the study. Compared to women, men had 1.78 increased likelihood of participating in a PMI study (95% CI=1.06, 2.98, p=0.03). No other sociodemographic factors had a significant association with the likelihood of participation. While respondents who were distrustful of researchers had a lower likelihood of participation compared to those who trusted investigators, this association was not statistically significant (OR=0.62, 95% CI=0.37, 1.04, p=0.07). Beliefs about positive expectations, concerns about privacy, and negative expectations about the impact of genetic research did not have significant associations with the likelihood of participation. These findings suggest that the way in which PMI research is described to potential subjects may be an important factor in participation decisions. The NCORP infrastructure can be used to determine the optimal ways to describe precision medicine studies to cancer patients by examining enrollment and retention rates across research that has different objectives, benefits, and participation requirements. Citation Format: Chanita Hughes Halbert. Conducting precision medicine research in the NCI Community Oncology Research Program. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr IA28.

Paving a Diverse and Emergency Medicine Centric Landscape for Clinical Trials and Research

To develop a strategy for recruiting African-American women into a research study for pregnant women. With few exceptions, NIH-funded investigators must include women and minorities in clinical research. The authors used the recommendations provided in the Outreach Notebook for the NIH Guidelines on Inclusion of Women and Minorities as Subjects in Clinical Research as a guide to help them reach out to African-American women in the community. The outreach experience led to a conference for African-American women about mental health. On the basis of this experience, the authors formulated a five-pronged approach for recruitment of African-American women into their study. The NIH guidelines were useful for this purpose.

To explore the role played by human research ethics committees (HRECs) with regard to the fair inclusion of men and women in Australian clinical research. Semi-structured face-to-face and telephone interviews with 25 chairs (or their nominees) of Australian HRECs between 9 June 2006 and 24 January 2007. Chairs' views about the role of HRECs in identifying sex discrimination, monitoring the inclusion of men and women in clinical research, and interpreting and applying National Health and Medical Research Council (NHMRC) guidelines relating to fair inclusion in research. In general, HRECs do not take an active role in monitoring the sex of research participants. They do not ask for or often receive information about the sex of participants. Most HREC chairs did not believe that sex discrimination in research is currently a significant or widespread problem, and were confident that their committees would be able to identify arbitrary exclusion of either men or women from research. However, many chairs expressed a lack of familiarity with debates about sex equity in research. Most chairs were unaware that anti-sex-discrimination legislation could apply to research. "Fair inclusion" was interpreted in a number of ways by chairs, but most frequently that the sex balance among research participants should reflect the sex distribution in the community of the condition under investigation. Chairs said their committees would be reluctant to reject a research protocol on the grounds that the sex balance among participants was perceived to be unfair. Views about, and expertise on, sex equity in research vary among chairs of HRECs. Many HRECs require further guidance about the appropriate standards for fair inclusion of men and women in Australian clinical research.

BackgroundBioethicists argue that inclusion of pregnant women in clinical research should be more routine to increase the evidence-base for pregnant women and foetuses. Yet, it is unknown whether pregnant women and others directly involved are willing to be routinely included. Therefore, we first need to establish what these stakeholders think about research participation in regular pregnancy-related research. However, studies on their views are scarce. In our study, we piggy-backed on a relatively conventional RCT, the APOSTEL VI study, to identify the views of stakeholders on inclusion of pregnant women in this study.MethodsWe conducted a prospective qualitative study using 35 in-depth semi-structured interviews and one focus group. We interviewed pregnant women (n = 14) recruited for the APOSTEL VI study, in addition to healthcare professionals (n = 14), Research Ethics Committee members (RECs) (n = 5) and regulators (n = 7) involved in clinical research in pregnant women.ResultsThree themes characterise stakeholders’ views on inclusion of pregnant women in the APOSTEL VI study. Additionally, one theme characterises stakeholders’ interest in inclusion of pregnant women in clinical research in general. First, pregnant women participate in the APOSTEL VI study for potential individual benefit and secondarily for altruistic motives, contrary to hypothetical studies. Second, a gatekeeping tendency hampers recruitment of pregnant women who might be eligible and willing, and questions about pregnant women’s decisional capacities surface. Third, healthcare professionals sometimes use the counselling conversation to steer pregnant women in a direction. Fourth, all stakeholders are hesitant about inclusion of pregnant women in clinical research in general due to a protective sentiment.ConclusionsPregnant women are willing to participate in the APOSTEL VI study for potential individual benefit and altruistic motives. However, an underlying protective sentiment, resulting in gatekeeping and directive counselling, sometimes hampers recruitment in the APOSTEL VI study as well as in clinical research in general. While bioethicists claim that inclusion of pregnant women should be customary, our study indicates that healthcare professionals, regulators, RECs and pregnant women themselves are not necessarily interested in inclusion. Advancing the situation and increasing the evidence-base for pregnant women and foetuses may require additional measures such as investing in the recruitment and feasibility of RCTs and stimulating pregnant women’s decisional capacities.

Quality clinical research remains a high priority during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) coronavirus disease (COVID-19) pandemic response, however, the logistical barriers of conducting research across institutions with differing departmental policy responses and varying resources is a documented problem.