Mollie W. Howerton

Barriers to Recruiting Underrepresented Populations to Cancer Clinical Trials : A Systematic Review

Racial and ethnic minorities, older adults, rural residents, and individuals of low socioeconomic status are underrepresented among participants in cancer‐related trials. The authors conducted a systematic review to determine the barriers to participation of underrepresented populations in cancer‐related trials. Their search included English‐language publications that reported original data on the recruitment of underrepresented groups to cancer treatment or prevention trials between 1966 and December 2005 in multiple electronic databases. They also hand‐searched titles in 34 journals from January 2003 to December 2005 and they examined reference lists for eligible articles. Titles and abstracts were reviewed to identify relevant studies. Data on barriers to participation were synthesized both qualitatively and based on statistically significant associations with trial enrollment. Of 5257 studies that were cited, 65 studies were eligible for inclusion in the current analysis, including 46 studies on recruitment into cancer therapeutic trials, 15 studies on recruitment into prevention trials, and 4 studies on recruitment into both prevention and treatment trials. Numerous factors were reported as barriers to participation in cancer‐related trials. However, only 20 of the studies reported statistically significant associations between hypothesized barriers and enrollment. The available evidence had limitations in quality regarding representativeness, justification of study methods, the reliability and validity of data‐collection methods, potential for bias, and data analysis. The results indicated that underrepresented populations face numerous barriers to participation in cancer‐related trials. The current systematic review highlighting the literature on recruitment of underrepresented populations to cancer trials and may be used as the evidence base toward developing an agenda for etiologic and intervention research to reduce the disparities in participation in cancer‐related trials. Cancer 2008.

Provider roles in the recruitment of underrepresented populations to cancer clinical trials

Providers play a vital role in the successful recruitment of underrepresented patients to cancer clinical trials because they often introduce the opportunity of clinical trials. The purpose of the current systematic review was to describe provider‐related factors influencing recruitment of underrepresented populations to cancer clinical trials.

Effectiveness of strategies to recruit underrepresented populations into cancer clinical trials

Background Certain populations, including racial and ethnic minorities and older persons, have had a history of low participation in cancer-related trials, yet there has been little information reported on recruitment strategies tailored to improve their enrollment. Methods We conducted a systematic literature review to examine the methods used to study recruitment of underrepresented populations into cancer prevention and treatment trials and examined the studies that compared the efficacy and/or effectiveness of different recruitment strategies. We performed an electronic search through multiple databases including PubMed and a hand search of 34 journals. Potential studies were pulled and underwent title, abstract, and article review by at least two investigators. Results Fourteen articles examined recruitment of underrepresented populations into cancer trials and, of these, five compared efficacy or effectiveness of different strategies for recruitment of underrepresented populations into randomized or concurrent controlled trials. These five studies used various strategies but only three reported that specific recruitment strategies, such as media campaigns and churchbased project sessions, resulted in improvement in accrual to cancer trials. Conclusion There is limited evidence for efficacious or effective strategies to recruit underrepresented populations in cancer-related trials. The available evidence cannot be generalized to these heterogeneous groups. Further study is needed on efficacious strategies for recruitment of underrepresented populations into cancerrelated trials.

Association between Lifestyle Factors and CpG Island Methylation in a Cancer-Free Population

Background: Many risk factors have been associated with cancer, such as age, family history, race, smoking, high-fat diet, and poor nutrition. It is important to reveal the molecular changes related to risk factors that could facilitate early detection, prevention, and overall control of cancer. Methods: We selected six cancer-specific methylated genes that have previously been reported in primary tumors and have also been detected in different bodily fluids of cancer patients. Here, we used quantitative fluorogenic real-time methylation-specific PCR in plasma DNA samples for the detection of methylation changes from an asymptomatic population who do not have any known cancer. Results: The promoter methylation frequencies of the studied genes were as follows: APC (7%), CCND2 (22%), GSTP1 (2%), MGMT (9%), RARβ2 (29%), and P16 (3%). Promoter methylation of at least one of the genes analyzed was observed in ∼46% (72 of 157) of the samples by binary dichotomization. Promoter hypermethylation of at least two genes was detected in 17% (26 of 157) of the samples. RARβ2 methylation was observed in 45% of subjects who had a high-fat diet in contrast with those who had a low-fat diet (23%; P = 0.007). Discussion: Our findings may help to elucidate early methylation changes that may lead to cancer development. These methylation changes could be due to exposure to risk factors and may be useful for cancer prevention measures such as changes in lifestyle. Longitudinal follow-up of a high-risk population is needed to understand the association of methylation of candidate genes in cancer development. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2984–91)

Defining "success" in recruitment of underrepresented populations to cancer clinical trials: Moving toward a more consistent approach

Although medically underserved groups bear a heavy burden of cancer disease and governmental agencies have required inclusion of minorities and women in cancer clinical trials since 1993, many of these groups are underrepresented in cancer prevention or treatment clinical trials. To assess and enhance recruitment of underrepresented populations into cancer‐related clinical trials, investigators and governmental agencies need consistent measurement approaches for recruitment that can be applied to diverse settings where trials are conducted. We conducted a systematic review to evaluate what measurement approaches were used to evaluate the success of recruitment of underrepresented groups into cancer prevention or treatment trials, and whether these recruitment goals were stated a priori. Only two articles reported an a priori recruitment goal. The recruitment measurement approaches varied considerably, with no consistent standard, especially for individual trials. By using the empiric evidence from this review in conjunction with the National Institutes of Health (NIH) guidelines, we constructed a framework for choosing consistent a priori recruitment goals for underrepresented groups based on the research question and study location. Using consistent measurement approaches for underrepresented groups will improve comparability of recruitment strategies across trials, improve equity in distribution of benefits and burdens of cancer‐related clinical trials, and may improve applicability of trial results to multiple populations. Cancer 2006.

Gender differences in correlates of colorectal cancer screening among black Medicare beneficiaries in Baltimore

Background: Previous research has shown colorectal cancer (CRC) screening disparities by gender. Little research has focused primarily on gender differences among older Black individuals, and reasons for existing gender differences remain poorly understood. Methods: We used baseline data from the Cancer Prevention and Treatment Demonstration Screening Trial. Participants were recruited from November 2006 to March 2010. In-person interviews were used to assess self-reported CRC screening behavior. Up-to-date CRC screening was defined as self-reported colonoscopy or sigmoidoscopy in the past 10 years or fecal occult blood testing in the past year. We used multivariable logistic regression to examine the association between gender and self-reported screening, adjusting for covariates. The final model was stratified by gender to examine factors differentially associated with screening outcomes for males and females. Results: The final sample consisted of 1,552 female and 586 male Black Medicare beneficiaries in Baltimore, Maryland. Males were significantly less likely than females to report being up-to-date with screening (77.5% vs. 81.6%, P = 0.030), and this difference was significant in the fully adjusted model (OR: 0.72; 95% confidence interval, 0.52–0.99). The association between having a usual source of care and receipt of cancer screening was stronger among males compared with females. Conclusions: Although observed differences in CRC screening were small, several factors suggest that gender-specific approaches may be used to promote screening adherence among Black Medicare beneficiaries. Impact: Given disproportionate CRC mortality between White and Black Medicare beneficiaries, gender-specific interventions aimed at increasing CRC screening may be warranted among older Black patients. Cancer Epidemiol Biomarkers Prev; 22(6); 1037–42. ©2013 AACR.

Applying justice in clinical trials for diverse populations

Background Considerable attention has focused on increasing clinical trial participation for members of “underrepresented groups”. However, doing so involves clarifying how to meet the demands of justice, or fairness, which provides the ethical mandate to enhance broad trial representation. Purpose To examine the ethical principle of justice as it applies to recruiting diverse populations to clinical trials representation. Methods In this paper, we analyse the conceptual and practical challenges in applying the principle of justice to clinical trials representation. Results Different facets of justice include demands for both fair outcomes and fair processes. Including both of these facets in clinical trials policy should not only promote access to trials, but also help to provide a framework to improve fairness in representation in clinical trials. Efforts to evaluate recruitment of representation should include outcome and process measures. Limitations The suggestions offered based on this conceptual analysis need to be tested empirically. Conclusions Those involved in the design, conduct and oversight of clinical trials should consider all of the facets of justice when assessing representation in clinical trials and attempt to balance fair access to trials with a fair process that may require protection from being unduly pressured to participate. Clinical Trials 2007; 4: 264—269; http://ctj.sagepub.com

Abstract B15: Effect of patient navigation on mammography screening among African American female Medicare beneficiaries at risk for low health literacy

Context: African American older adult women are diagnosed with more advanced breast cancer and have lower survival rates than White women. While differences in health literacy may contribute to this disparity, there is limited information on intervention strategies to promote cancer screening among low-literate African American older adults. Objective: To evaluate the effect of a patient navigator on adherence to mammography screening among African American female Medicare beneficiaries with low literacy scores. Design, Setting, and Participants: We analyzed data from the Cancer Prevention and Treatment Demonstration (CPTD) at Johns Hopkins, an ongoing community-based trial designed to determine whether patient navigation is an effective strategy for improving adherence to cancer screening among African American older adults. Participants are randomized to either a high intensity group (patient navigation = educational materials) or a low intensity group (educational materials only). This analysis included 272 women ages of 65 and older with low literacy scores, who were enrolled into the study between November 2006 and March 2010, and had at least one year of follow up data. Baseline and one year follow up interviews were conducted face to face by trained interviewers through standardized questionnaires. The REALM-R instrument was used to identify participants at risk for low health literacy, based on their score. Main Outcome Measure: The outcome measure for this analysis was the between-group difference in the proportion of women receiving mammography screening during the follow up period. Multiple logistic regression was performed to control for potential confounders such as age, education, Medicaid coverage, and perceived health status. Results: Compared to the educational materials only group (n=77), the patient navigation group (n=107) had a similar proportion of women who reported a mammogram at one year follow up (64% vs. 71 %, p-value = 0.32). However, after adjusting for baseline health and demographic characteristics, women in the patient navigation group were more likely to report a mammogram at one year follow up, compared to those in the educational materials group (OR 1.90 95% CI 1.01-3.54). Women who rated themselves as having excellent to good health at baseline were less likely to report a mammogram, than those who reported fair to poor health (OR 0.43 95% CI 0.21-0.87). Conclusions: Use of a patient navigation-based intervention was positively associated with mammography screening adherence among African American older adult women with low literacy scores. In this study population, perception of health status may influence mammography screening adherence. Our findings underscore the need for tailored intervention strategies to reduce cancer screening disparities among low-literate African American older adults. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B15.

Authors' response to J Kahn

We appreciate Dr Kahn’s attention to seeking conceptual clarity between the ethical principles of justice and respect for autonomy (or persons). He argues that our application of the principle of justice overextends its reach. In particular, he takes issue with the fair process portion of our account, worrying that it encroaches on the ethical territory usually occupied by the principle of respect for autonomy. Granted, justice ought never to be confused with respect for autonomy. However, it is one thing to ensure an individual’s autonomous authorization for research participation (i.e., respect for autonomy as may be manifested through the process of informed consent); it seems quite another thing to ensure that the system of recruitment (the means) is set up and conducted in a fair manner. As such, we maintain that the principle of justice demands attention to both the fair means (processes) and ends (outcomes) of research recruitment. Fairness as a system characteristic in the implementation of research strikes us as basic to responsible research that has very little to do with ensuring the fair distribution of research outcome benefits. Furthermore, such an account is consistent with scholarship in legal theory that distinguishes ‘distributive justice’ from ‘procedural justice’. Finally, the Belmont Report to which Dr Kahn appeals would seem to endorse our view: ‘the principle of justice gives rise to moral requirements that there be fair procedures and outcomes in the selection of research subjects’. To deny fair process considerations risks concluding that fair outcomes are the only relevant standards of judging whether research is just. We hope our account promotes further dialogue about fairness in research.