Pragmatic patient engagement in designing pragmatic oncology clinical trials.

Oncology trials are the cornerstone of effective and safe therapeutic discoveries. However, there is increasing demand for pragmatism and patient engagement in the design, implementation and dissemination of oncology trials. Many researchers are uncertain about making trials more practical and even less knowledgeable about how to meaningfully engage patients without compromising scientific rigor to meet regulatory requirements. The present work provides practical guidance for addressing both pragmaticism and meaningful patient engagement. Applying evidence-based approaches like PRECIS-2-tool and the 10-Step Engagement Framework offer practical guidance to make future trials in oncology truly pragmatic and patient-centered. Consequently, such patient-centered trials have improved participation, faster recruitment and greater retention, and uptake of innovative technologies in community-based care.

Lessons Learned from the Medical University of South Carolina Transdisciplinary Collaborative Center (TCC) in Precision Medicine and Minority Men's Health.

The Transdisciplinary Collaborative Center (TCC) in Precision Medicine for Minority Men's Health was established at the Medical University of South Carolina (MUSC) in 2015 to address disparities in the translation of precision medicine approaches among racial minority groups. This regional consortium focuses on three primary areas: (1) the development of a consortium of regional and national partners, (2) conducting transdisciplinary research examining synergistic effects of biological, social, physiological, and clinical determinants of chronic disease risks and outcomes, and (3) dissemination and implementation of precision medicine approaches, with an emphasis on reducing disparities in health care and outcomes among minority men. Given consistent calls to better translate precision medicine approaches and the focus of this consortium on addressing disparities among minority men, we provide an overview of our experience in developing the MUSC TCC, including barriers and facilitators to conducting translational research on minority men's health issues in the context of precision medicine. Lessons learned and areas for improvement include providing enough time to create consistent partnerships and community engagement to improve recruitment and retention, identifying unique ways to engage diverse partners from across the region and nation, and better approaches to dissemination and communication for large partnerships focusing on precision medicine.

A Legacy of Science and Community Engagement via the Community Networks Program.

This special issue documents the progress of a unique group of research investigations that further legitimize the engagement of affected communities in quality cancer health disparities research and, the importance of mentoring and training of new and diverse health disparity researchers. The implications for the reduction and elimination of cancer health disparities within the United States are apparent. The diversity of populations included in these novel studies also has implications for addressing inequities in a global context.

The National Cancer Institute's Community Networks Program Initiative to Reduce Cancer Health Disparities: Outcomes and Lessons Learned.

BACKGROUND: We describe reach, partnerships, products, benefits, and lessons learned of the 25 Community Network Programs (CNPs) that applied community-based participatory research (CBPR) to reduce cancer health disparities. METHODS: Quantitative and qualitative data were abstracted from CNP final reports. Qualitative data were grouped by theme. RESULTS: Together, the 25 CNPs worked with more than 2,000 academic, clinical, community, government, faith-based, and other partners. They completed 211 needs assessments, leveraged funds for 328 research and service projects, trained 719 new investigators, educated almost 55,000 community members, and published 991 articles. Qualitative data illustrated how use of CBPR improved research methods and participation; improved knowledge, interventions, and outcomes; and built community capacity. Lessons learned related to the need for time to nurture partnerships and the need to attend to community demand for sustained improvements in cancer services. IMPLICATIONS: Findings demonstrate the value of government-supported, community-academic, CBPR partnerships in cancer prevention and control research.

The Affordable Care Act and genetic testing for inheritable cancer syndromes: impact on high-risk underserved minorities.

Genetic testing for inheritable cancer syndromes is becoming a critical part of preventive health services. The Patient Protection and Affordable Care Act (PPACA) Essential Health Benefits package addresses breast cancer susceptibility-gene testing for women who are unaffected by cancer. The absence of provisions for 1) men, 2) cancer patients, 3) other inheritable cancer syndromes, and 4) risk-reducing interventions are limitations of PPACA. We discuss provisions and limitations of PPACA pertaining to genetic testing and effects on high-risk populations, in particular minorities. The PPACA is the beginning of an ongoing process of incorporating genetic testing in the armamentarium of cancer prevention. Future efforts should focus on ensuring equitable access to genetic testing as a preventive service under PPACA to high-risk populations other than women. Consideration should also be given to provisions for risk-reducing interventions, especially in underserved minority populations, who are known to underutilize genetic testing and may have limited financial resources for medical intervention.

A model for bidirectional community-academic engagement (CAE): overview of partnered research, capacity enhancement, systems transformation, and public trust in research.

The University of Maryland's Office of Policy and Planning in collaboration with urban and rural community partners, planned and implemented a model for community-academic engagement (CAE) in partnered research and programs. The model addressed health disparities, cancer and tobacco-related diseases, and public trust in research. Environments have flourished that resulted in bidirectional community-academic interactions, and led to transformation of the academic environment and community capacity to identify and address health issues. This collaborative model produced: •    enhanced public trust in research; and •    enhanced community and Academic Health Center (AHC) capacity to address community health needs as partners. A unique feature of this model is AHC's shared grant funding with community partners serving diverse and medically underserved communities for predetermined roles in research, policy and educational programs. Over $18 million in grant funding was provided to community organizations. This paper presents an overview of this model as a case study.

Prostaglandin E receptor EP1 suppresses breast cancer metastasis and is linked to survival differences and cancer disparities.

Cyclooxygenase-2 is frequently overexpressed and associated with poor prognosis in breast cancer. The cyclooxygenase-2 product prostaglandin E(2) elicits cellular responses through four G-protein-coupled receptors, designated EP1 to EP4, coupled to distinct intracellular signaling pathways. EP4, expressed on malignant breast cells, promotes metastasis; however, a role for EP1 in metastasis has not been investigated. Using a murine model of metastatic breast cancer, we now show that pharmacologic antagonism of EP1 with SC19220 or AH6809 promoted lung colonization of mammary tumor cells by 3.7- to 5.4-fold. Likewise, reducing EP1 gene expression by shRNA also increased metastatic capacity relative to cells transfected with nonsilencing vector but did not affect the size of transplanted tumors. Examination of invasive ductal carcinomas by immunohistochemistry shows that EP1 was detected in both the cytoplasm and nucleus of benign ducts as well as malignant cells in some samples, but was absent or limited to either the nucleus or cytoplasm in other malignant samples. Overall survival for women with tumors that were negative for nuclear EP1 was significantly worse than for women with EP1 expression (P = 0.008). There was no difference in survival for women with differences in cytoplasmic EP1 expression (P = 0.46). Comparing EP1 mRNA in breast tumors from African American and European American women revealed that many more African American breast tumors lacked detectable EP1 mRNA (P = 0.04). These studies support the hypothesis that EP1 functions as a metastasis suppressor and that loss of nuclear EP1 is associated with poorer overall survival and may contribute to disparities in outcome in different populations.

Tobacco smoke exposure in either the donor or recipient before transplantation accelerates cardiac allograft rejection, vascular inflammation, and graft loss.

BACKGROUND: Tobacco exposure in cardiac transplant recipients, before and after transplantation, may increase the risk of cardiac allograft vasculopathy and allograft loss, but no direct evidence for this phenomenon is forthcoming. In this experimental study, we investigated early consequences of tobacco smoke exposure in cardiac transplant donors and recipients with an emphasis on alloinflammatory mediators of graft outcome. METHODS AND RESULTS: Using heterotopic rat cardiac transplantation, we tested the effects of donor or recipient tobacco smoke exposure in 6 groups of animals (rat heterotopic cardiac transplantation) as follows: tobacco-naïve allogeneic rejecting controls (n=6), tobacco-naïve nonrejecting controls (n=3; killed on day 5 to simulate survival times of tobacco-treated animals), isografts (n=3), both donor and recipient rats exposed to tobacco smoke (n=4), only donor rats exposed to tobacco smoke (n=7), and only recipient rats exposed to tobacco smoke (n=6). Polymerase chain reaction studies of tissue and peripheral (systemic) protein expression were performed to evaluate inflammatory (tumor necrosis factor-alpha, interferon-gamma, interleukin-6) and alloimmune (interleukin-1 receptor 2, programmed cell death-1, and stromal cell-derived factor-1) pathways, as was histological analysis of the cardiac allografts. Our experiments reveal that pretransplantation tobacco exposure in donors and/or recipients results in heightened systemic inflammation and increased oxidative stress, reduces posttransplantation cardiac allograft survival by 33% to 57%, and increases intragraft inflammation (tumor necrosis factor-alpha, interferon-gamma, interleukin-6) and alloimmune activation (CD3, interleukin-1 receptor 2, programmed cell death-1, and stromal cell-derived factor-1) with consequent myocardial and vascular destruction. CONCLUSIONS: These sentinel findings confirm that tobacco smoke exposure in either donors or recipients leads to accelerated allograft rejection, vascular inflammation, and graft loss. Molecular pathways that intersect as arbiters in this phenomenon include instigation of alloimmune activation associated with tobacco smoke-induced inflammation.

A descriptive analysis of state legislation and policy addressing clinical trials participation.

OBJECTIVES: This report describes state policy and legislation related to clinical trials participation and Maryland's model to enhance clinical trial availability and participation. METHODS: Descriptive review of state policy and legislation related to coverage for clinical trials costs based on data from the National Cancer Institute (NCI) State Cancer Legislative Database, the American Cancer Society, and NCI; additionally, discussion of Maryland's comprehensive multilevel clinical trial model comprising policy initiatives, community engagement, research, education, and infrastructure support. RESULTS: Twenty-four states have mandated clinical trial coverage through specific legislation or agreements since 1994. Covered benefits varied among the states. CONCLUSIONS: Besides cost and insurance barriers, there is a need to address important patient, physician and researcher, and structural barriers to clinical trial participation. Maryland provides a comprehensive model to address the multi-faceted clinical trial participation determinants as it tracks state and federal policy, documents trial barriers, and conducts community education.

Increasing pap smear utilization among Samoan women: results from a community based participatory randomized trial.

BACKGROUND: We tested the effectiveness of a theory-guided, culturally tailored cervical cancer education program designed to increase Pap smear use among Samoan women residing in the U.S. Territory of American Samoa. METHODS: We used a two-group, pretest-posttest design. The sample comprised 398 Samoan women age 20 and older recruited from Samoan churches. Women in the intervention group received a culturally tailored cervical cancer education program in three weekly sessions. The primary outcome was self-reported receipt of a Pap smear. RESULTS: Overall, there was a significant intervention effect, with intervention compared with control group women twice (adjusted odds ratio = 2.0, 95% confidence interval = 1.3-3.2, p < .01) as likely to self-report Pap smear use at the posttest. CONCLUSIONS: The findings support the efficacy of the multifaceted, theory-guided, culturally tailored community-based participatory cervical cancer education program for Samoan women in effecting positive changes in Pap smear use and cervical cancer related knowledge and attitudes.

Analysis of Maryland cancer patient participation in National Cancer Institute-supported cancer treatment clinical trials.

PURPOSE: We examined the relationship of sociodemographic factors, urban/rural residence, and county-level socioeconomic factors on accrual of Maryland patients with cancer to National Cancer Institute (NCI)-sponsored cancer treatment clinical trials. PATIENTS AND METHODS: Data were analyzed for the period 1999 to 2002 for 2240 Maryland patients with cancer accrued onto NCI-sponsored treatment trials. The extent to which Maryland patients with cancer and patients residing in lower socioeconomic and/or rural areas were accrued to cancer trials and were representative of all patients with cancer in Maryland was determined. Data were obtained from several sources, including NCI's Cancer Therapy Evaluation Program for Maryland patients with cancer in Cooperative Group therapeutic trials, Maryland Cancer Registry data on cancer incidence, and United States Census and the Department of Agriculture. RESULTS: For Maryland patients with cancer accrued onto NCI-sponsored treatment trials between 1999 and 2002, subgroups accrued at a higher rate included pediatric and adolescent age groups, white patients, female patients (for sex-specific tumors), patients with private health insurance, and patients residing in the Maryland National Capitol region. Moreover, between 1999 and 2002, there was an estimated annual decline (8.9% per year; P < .05) in the percentage of black patients accrued onto cancer treatment trials. Logistic regression models uncovered different patterns of accrual for female patients and male patients on county-level socioeconomic factors. CONCLUSION: Results highlight disparities in the accrual of Maryland patients with cancer onto NCI-sponsored treatment trials based on patient age, race/ethnicity, geography of residence, and county-level socioeconomic factors. Findings provide the basis for development of innovative tailored and targeted educational efforts to improve trial accrual, particularly for the underserved.

Adverse effects of nicotine and immunosuppression on proximal tubular epithelial cell viability, tissue repair and oxidative stress gene expression.

BACKGROUND: Renal dysfunction in non-renal transplantation is a major arbiter of poor late allograft outcomes. Tobacco recidivism is an important modifiable risk marker for cardiac allograft loss, but its effects on renal dysfunction remain poorly studied. METHODS: In a 96-well plate, 10(-5) proximal tubular epithelial (PTE) cells (HK-2, American Type Culture Collection) were cultured overnight and treated with sirolimus (SRL; 100 nmol/liter), nicotine (N; 10(-7) mol/liter) and mycophenolate mofetil (MMF; 10 micromol/liter), alone or in combination for 24 hours. Cell viability was quantified by treatment with tetrazolium salt WST-1 and calculated as the difference in percent inhibition with respect to the optical densitometry (OD) of treated and untreated cells. Gene and protein expression was analyzed using real-time polymerase chain reaction and Western blot techniques. RESULTS: OD decreased with SRL (-52.7 +/- 2.85%), N (-47.3 +/- 3.84%) and MMF (-53.3 +/- 2.4%) in isolation. Further reduction in OD occurred when N was combined with SRL (-63 +/- 2.3%, p < 0.04), MMF (-64.3 +/- 1.45%, p < 0.02) or the combination of SRL and MMF (-78.2%, p < 0.007). Compared with control, treatment of PTE cells with N increased mRNA expression of transforming growth factor-beta (TGF-beta; 10-fold), connective tissue growth factor (CTGF; 25-fold), osteopontin (OPN; 10-fold) and NADPH oxidase components (p22(phox), NOX-1 and Rac-1 at 18-, 16- and 12-fold, respectively). The pre-treatment of cells with inhibitor of superoxide generator diphenylene iodonium (DPI) reversed these effects. CONCLUSIONS: Nicotine adversely amplified the effects of SRL and MMF on tissue repair and oxidative stress markers, subsequently modulating PTE viability. However, caution is advised in extrapolating these in vitro findings to the human model.

Clinical trials: the art of enrollment.

OBJECTIVES: Enrollment barriers and multidisciplinary approaches to increase cancer trials participation are presented. Recruitment barriers, research in Maryland, and a Best Practice for cancer trials are discussed. DATA SOURCES: Journal and research articles, web sites. CONCLUSION: Clinical trials have produced prevention and care advances for cancer and other diseases. Trial enrollment is lower for minorities and underserved communities. A comprehensive program for addressing enrollment barriers should incorporate research on barriers, multidisciplinary teams, and education and trial infrastructure in community settings. IMPLICATIONS FOR NURSING PRACTICE: Health disparities training, including culturally appropriate enrollment approaches for education and retention of underserved communities, should incorporate community stakeholders and nurse/physician researchers.

A randomized trial comparing web-based decision aids on prostate cancer knowledge for African-American men.

OBJECTIVES: Few decision aids are tailored for African-American men. We sought to determine if web-based decision aids increased knowledge of prostate cancer screening among African men. METHODS: This postintervention, quasiexperimental research measured knowledge of prostate cancer screening among African-American men following receipt of 1 of 2 web-based decision aids: enhanced or usual care. Men ages 40-65 were recruited at the annual convention of the Prince Hall Masons in the summer of 2007, which was attended by 1170 masons. The primary outcome was knowledge of prostate cancer screening. RESULTS: There were 87 participants in the sample with a mean age of 52 years (standard deviation = 6.9). Forty-six masons were randomized to the enhanced decision aid, and 41 masons were randomized to the usual care decision aid. Knowledge scores were statistically significantly higher among the men receiving the enhanced decision aid compared to the usual care decision aid after simultaneously adjusting for age, educational level, marital status, family history, previous prostate specific antigen test and digital rectal exam (p = 0.01). CONCLUSION: We found evidence that the enhanced web decision aid was significantly more effective than the usual care decision aid in promoting knowledge of the benefits, limitations and risks of prostate cancer screening. Web-based sites may be effective in facilitating discussions about screening between patients and health care providers.

Analysis of Maryland cancer patient participation in national cancer institute-supported cancer treatment clinical trials.

PURPOSE: We examined the relationship of sociodemographic factors, urban/rural residence, and county-level socioeconomic factors on accrual of Maryland patients with cancer to National Cancer Institute (NCI) -sponsored cancer treatment clinical trials. PATIENTS AND METHODS: Data were analyzed for the period 1999 to 2002 for 2,240 Maryland patients with cancer accrued onto NCI-sponsored treatment trials. The extent to which Maryland patients with cancer and patients residing in lower socioeconomic and/or rural areas were accrued to cancer trials and were representative of all patients with cancer in Maryland was determined. Data were obtained from several sources, including NCI's Cancer Therapy Evaluation Program for Maryland patients with cancer in Cooperative Group therapeutic trials, Maryland Cancer Registry data on cancer incidence, and United States Census and the Department of Agriculture. RESULTS: For Maryland patients with cancer accrued onto NCI-sponsored treatment trials between 1999 and 2002, subgroups accrued at a higher rate included pediatric and adolescent age groups, white patients, female patients (for sex-specific tumors), patients with private health insurance, and patients residing in the Maryland National Capitol region. Moreover, between 1999 and 2002, there was an estimated annual decline (8.9% per year; P < .05) in the percentage of black patients accrued onto cancer treatment trials. Logistic regression models uncovered different patterns of accrual for female patients and male patients on county-level socioeconomic factors. CONCLUSION: Results highlight disparities in the accrual of Maryland patients with cancer onto NCI-sponsored treatment trials based on patient age, race/ethnicity, geography of residence, and county-level socioeconomic factors. Findings provide the basis for development of innovative tailored and targeted educational efforts to improve trial accrual, particularly for the underserved.

Breast cancer epidemiology in blacks and whites: disparities in incidence, mortality, survival rates and histology.

BACKGROUND: This study presents black-white breast cancer statistics, tumor histology and receptor status, and treatment patterns for all ages and by age groups (< 40, 40-49, and > or = 50). METHODS: The study used data from the National Cancer Institute (NCI) Surveillance, Epidemiology and End Results (SEER) program for the time period 1995-2004. Age-adjusted incidence, mortality, relative survival rates, tumor grade, histology and receptor status, and treatment patterns for invasive breast cancer were calculated for nine SEER cancer registries for 1995-2004. RESULTS: Invasive breast cancer age-adjusted incidence for black women age < 40 was significantly higher than those for white women (rate ratio = 1.16, 95% confidence interval: 1.10-1.23). Age-adjusted mortality rate for black women age < 40 was twice that for white women. Compared to white women, black women were significantly more likely to be diagnosed with regional or distant disease, have lower relative five-year survival rate and have higher likelihood of being diagnosed with tumors with poorer prognosis. Black women were less likely to receive breast cancer surgery as part of the treatment plan. CONCLUSIONS: Race/ethnic disparities in invasive breast cancer epidemiology, prognostic indicators and treatment patterns exist between black and white women. The study findings support the need for innovative research, especially on the multifaceted determinants of the differential epidemiology of breast cancer. Equally important, there is a need for evidence-guided equal delivery of quality care to eliminate breast cancer disparities among black women.

Results of a randomized trial to increase mammogram usage among Samoan women.

BACKGROUND: There are no effective breast cancer education programs targeting Samoan women. We tested the effectiveness of a theory-guided, culturally appropriate breast cancer education program (the intervention) designed to increase mammography use among Samoan women. METHODS: This community-based participatory cluster-randomized controlled intervention trial used a parallel two-group design. The sample consisted of 776 women aged 42 and older who had not had a mammogram in the preceding 2 years. The primary outcome was self-reported mammogram use between pretest and posttest. RESULTS: Overall, there was no statistically significant intervention effect, although the odds of self-reported mammogram use were higher in the intervention than the control group (odds ratio (OR), 1.26; 95% confidence interval (95% CI), 0.74, 2.14; P = 0.39). Exploratory subgroup analyses found that the intervention was effective only among women who were aware of mammograms but had never previously obtained one (OR, 1.99; 95% CI, 1.03, 3.85; P = 0.04). Low need for social support and lack of endorsement of culture-specific beliefs about breast cancer were associated with mammogram use in this group. In women unaware of mammography at pretest, high perceived susceptibility to breast cancer and endorsement of culture-specific beliefs were associated with mammogram use. For women who had previously obtained a mammogram, lower self-efficacy was associated with mammogram use. Intervention compared with control group women had significantly higher levels of knowledge of risk factors and lower endorsement of culture-specific beliefs at posttest. CONCLUSIONS: Results suggest that a multifaceted education intervention may improve mammogram usage for certain subgroups of Samoan women.

Mammography screening and Pacific Islanders: role of cultural and psychosocial factors.

BACKGROUND: There is little information on the associations between cultural and psychosocial factors and not receiving a mammogram by Samoan women. METHODS: Survey of 809 Samoan women aged 42 years and older. RESULTS: The likelihood of nonreceipt was lower for women who had higher perceptions of severity, agreement with a mammogram's efficacy, higher group norms, higher self-efficacy, and those who placed greater importance on the breast. The likelihood of nonreceipt was higher for women who harbored misconceptions and endorsed culture-specific beliefs. CONCLUSIONS: Samoan women need specifically tailored breast cancer education which incorporates cultural and psychosocial factors important for behavior change.

Maryland's Special Populations Network. A model for cancer disparities research, education, and training.

The unequal burden of cancer in minority and underserved communities nationally and in Maryland is a compelling crisis. The Maryland Special Populations Cancer Research Network (MSPN) developed an infrastructure covering Maryland's 23 jurisdictions and Baltimore City through formal partnerships between the University of Maryland School of Medicine, University of Maryland Statewide Health Network, University of Maryland Eastern Shore, and community partners in Baltimore City, rural Eastern Shore, rural Western Maryland, rural Southern Maryland, and Piscataway Conoy Tribe and statewide American Indians. Guided by the community-based participatory framework, the MSPN undertook a comprehensive assessment (of needs, strengths, and resources available) that laid the foundation for programmatic efforts in community-initiated cancer awareness and education, research, and training. The MSPN infrastructure was used to implement successful and innovative community-based cancer education interventions and technological solutions; conduct education and promotion of clinical trials, cancer health disparities research, and minority faculty cancer research career development; and leverage additional resources for sustainability. MSPN engaged in informed advocacy among decision- and policymakers at state and national levels, and its community-based clinical trials program was recognized by the U.S. Department of Health and Human Services as a Best Practice Award. The solutions to reduce and eliminate cancer health disparities are complex and require comprehensive and focused multidisciplinary cancer health disparities research, training, and education strategies implemented through robust community-academic partnerships. Cancer 2006. (c) American Cancer Society.

Recruitment and participation in clinical trials: socio-demographic, rural/urban, and health care access predictors.

BACKGROUND: Recruitment and participation in clinical trials by minorities, particularly African Americans and rural underserved populations, are low. This report examines predictors of clinical trial recruitment and participation for adult Marylanders. METHODS: A cross-sectional design was used to survey 5154 adults (18 years and older) residing in 13 of the 24 jurisdictions in Maryland, including urban Baltimore City, and the rural regions of Western Maryland and the Eastern Shore. The survey, conducted between December 2001 and March 2003, used Computer-Assisted Telephone Interviewing and random-digit dialing procedures. Primary dependent variables included "ever asked to participate" (i.e., recruited) and "participated" in clinical trials. RESULTS: 11.1% of the respondents had been recruited to clinical trials. In addition, 59.4% of the respondents recruited to clinical trials actually participated in a clinical trial. Among respondents recruited to clinical trials, black and middle income respondents were significantly less likely to actually participate in clinical trials; whereas, respondents who received information about clinical trials from their health care provider, who were knowledgeable about clinical trials, and those who had the time commitment were significantly more likely to participate in clinical trials. CONCLUSIONS: These results suggest serious gaps in efforts to recruit racial/ethnic minorities and residents of rural regions into clinical trials. The findings provide the basis for the development and implementation of community-based educational programs for both the general public and health care professionals, and to enhance availability of community-based clinical trials, especially in the rural areas of the state.