#91404: Clinical Trials: Considerations for Women and Ethnic Minorities

Clinical trial registries are not a new phenomenon; they have existed for decades [9]. These registries are database systems that list up-to-date information about different federally and privately funded clinical trials. They give the public information about both current and completed clinical trials. The public can access information about the purpose of the clinical trial, locations, and contact information. One of the main goals of these registries is to promote transparency in the conduction of clinical trials and their findings [113].

One of the largest registries in the world is ClinicalTrials.gov, which includes both national and international clinical trials [10]. ClinicalTrials.gov was started in 1999 by the National Institute of Health [113]. Within several years, many top medical journals would not review, accept, or publish manuscripts of clinical trials that were not included in this registry [114]. Today, registered clinical trials must also submit their findings [114].

Examples of other clinical trial registries include:

Since the implementation of the NIH Revitalization Act, many researchers have examined gender reporting and the inclusion of women in medical studies. Many have concluded there are still gender disparities and that progress has been slow [142]. Women are less likely than men to be enrolled in colorectal cancer, lung cancer, and surgical oncology clinical trials sponsored by the National Cancer Institute [204]. As recently as 2015, the U.S. Government Accountability Office maintained that gender differences must be taken into account in clinical research and [171]. A meta-analysis of randomized clinical trials of adult cardiac surgical procedures published between 2000 and 2020, identified 51 trials representing a total of 25,425 participants [205]. In 2000, 29.6% of the study sample were women, but this dropped to 13% in 2019. Similarly, a meta-analysis of five diabetes cardiovascular outcomes trials involving 46,606 participants found that women were under-represented, comprising 28.5% to 35.8% of the population in each study [206].

In an analysis of oncology clinical trials, female research subjects represented 39% of all lung cancer trial participants, despite the fact that women have a higher prevalence of lung cancer [172]. This was also true of melanoma (35%) and pancreatic (40%) clinical trials. In a 2018 meta-analysis of randomized controlled trials published in American medical journals (782 studies in 14 journals), 15% of the studies had enrolled less than 30% women [173].

In 2013, a meta-analysis of 304 cancer clinical trials that included women found that more than 80% of the published studies reported a white sample and 60% of the participants were male subjects [146]. Concerns remain about gender and racial disparities in clinical trial participation.

In a 2011 systematic review of publications of phase III clinical trials, only 28% of the studies made any specific reference to gender [119]. However, there has been an increase in enrollment of women in these clinical trials as the average enrollment was 37% during this time period. Although it seems as if the NIH Revitalization Act has perhaps helped increase the enrollment of women, this has not appeared to have led to detailed reporting of the impact of the interventions on women nor "whether there is or is not a significant difference of clinical or public health importance between males and females in relation to the study variables" [119].

In another study, published NIH-funded studies in four leading medical journals in 1993, 1995, 1997, and 1999 were examined to determine if women were included and if the statistical analyses took gender into account [27]. Approximately one-fifth of the studies did not include women at all, and between one-quarter and one-third of the studies analyzed the findings by gender. The authors conducted follow-up telephone interviews with the original researchers of the published studies. Of the 18 researchers who were interviewed, 6 indicated that they did not analyze the data by gender because the sample size was too small for such an analysis. One researcher indicated that sex differences were well known in the topic area, and consequently, they decided it was not worthy of publishing.

A 2001 study examined patterns of enrollment by gender in randomized clinical trials by reviewing national and international studies published in the New England Journal of Medicine between 1994 and 1999 [28]. During this time, 120 randomized clinical trials met the eligibility criteria of the study. Of these studies, the authors found an average of 24.6% of participants were women, and only 14% of the studies analyzed the data based on gender. The authors concluded the Revitalization Act had minimal influence, both in the United States and internationally. Experts argue that much progress is needed in the area of recruitment of women. This includes making concerted efforts for inclusion and providing necessary resources (e.g., transportation, childcare, etc.) to make it more amenable for women to participate in clinical trials [27].

In a study of published articles on federally funded randomized control studies during 2004, researchers found that women were under-represented in these studies, comprising about 37% of the sample [29]. Gender was not taken into account in 87% of the studies, and 87% did not conduct any analysis by racial or ethnic groups.

A 2007 study focused on sex-specific reporting in articles on cardiovascular trials published in leading medical and cardiology journals during a six-month period from July to December 2004 [30]. The researchers found that three-quarters of the studies did not report differences in findings between male and female participants. Approximately 7% did not list the sex of participants, and 3% did not include women in their clinical trials [30].

By far, white, married, middle-class, and well-educated men are the largest segment of the population who participate in clinical trials and health-related research [31]. The NIH Revitalization Act of 1993 was implemented with the goal of changing this trend. This law has increased the number of minority participants in NIH-sponsored clinical trials, from approximately 1 million minority research subjects in 1995 to almost 15 million in 2016 [174]. However, this gain is almost entirely the result of greater number of trials and larger trials, as the rate of racial and ethnic minority participation has remained relatively level (36.7% in 1995 compared with 37.2% in 2016) [174]. One study examined the extent to which racial minorities were represented in U.S. vaccine clinical trials between 2011 to 2020 [207]. In total, 230 trials met the inclusion criteria, with a total of 219,555 research subjects. Nearly 78% of participants were White, 11.6% were Hispanic, 10.6% were Black/African American, 5.7% were Asian American, and 0.4% were Native American/American Indian.

Black/African Americans represent 12.3% of the U.S. population, but they only represented 9.7% and 9.8% in the Moderna and Pfizer COVID-19 vaccine clinical trials, respectively. Conversely, 73.6% of the U.S. population is White, but their participation rates in the Moderna and Pfizer trials were 79.4% and 81.9%, respectively [208].

In 20 health studies representing 700,000 participants that reported consent rates by ethnicity and race, researchers found that the consent rates did not differ significantly according to ethnicity and race [32]. However, they did find that in some studies, ethnic minorities were offered fewer opportunities to participate compared to their white counterparts. Relatedly, cancer clinical trials enrollment and participation among African Americans and Hispanics declined between 1996 and 2002 [33].

This pattern is observed in the many different types of clinical trials. For example, in clinical trials of HIV drugs, racial and ethnic minorities have traditionally been under-represented. A survey study of 266 HIV patients receiving services at an urban hospital indicated that racial and ethnic minorities were less likely to participate in HIV clinical trials compared to other HIV-diagnosed patients [34]. Latino patients were more likely to indicate that they were not informed about clinical trials. In a study of clinical trials for pulmonary diseases, only a modest increase in the inclusion of racial and ethnic minorities in non-NIH funded clinical trials was noted between 1993 and 2013 (1.1% to 3%, respectively) [165]. The largest increase was among Asians or Asian Americans (0.2% to 1.9%) [165].

Another issue is lack of reporting on participant race/ethnicity. In a meta-analysis of oncology clinical trials 2003 and 2016 (1,012 trials), only 31% reported race/ethnicity [172]. Among these trials, the majority of participants (83.4%) were non-Hispanic white, while 5.9% were black/African American, 5.3% were Asian/Pacific Islander, 2.6% were Hispanic, and 0.3% were Native American.

Racial and ethnic minorities also generally perceive that clinical trials are not necessarily targeted to them as a group. A focus group study found that African Americans and Native Americans felt that they did not fit into the typical profile of those who participated in clinical trials. They described typical study subjects as those from middle or upper socioeconomic brackets, holding at least a high school diploma, and being well connected in their communities [35]. Participants also fear being exploited and may refer to past atrocities (e.g., the Tuskegee study) [175].

In a 2014 meta-analysis, researchers found that less than 2% of the National Cancer Institute's clinical trials included racial and ethnic minority research subjects as their primary sampling [147]. Furthermore, only 20% of the randomized control studies in peer-reviewed oncology journals analyzed findings based on race and ethnicity. In FDA cancer therapy clinical trials conducted between 2008 and 2018, only 25% reported race subgroups in their analyses [209].

In a 2011 meta-analysis, researchers found that there was minimal improvement in reporting sex and race/ethnicity in clinical trial publications compared to 2004, with only 21% including outcomes data by race/ethnicity [120]. Among those that did report race/ethnicity data, African American and Hispanic research subjects were under-represented relative to their overall proportion in the U.S. population.

In a meta-analysis of trials funded by the National Institute of Mental Health (NIMH) between 1995 and 2004, the great majority (91.6%) reported gender and almost three-quarters of the studies reported race or ethnicity of participants [36]. But, more than half of the studies did not provide a complete breakdown of participants by race and ethnicity, and almost 90% of these studies only reported the number of white participants compared to non-white participants.

It should be noted that there is tremendous diversity within racial/ethnic groups, and race as a single primary variable to explain differences should be avoided. For example, when socioeconomic status or other demographic variables are taken into account along with race, race is no longer a significant variable [121]. In addition, acculturation and assimilation should be considered when analyzing the role of race and ethnicity.

In summary, clinical trial participation rates among women and racial/ethnic minorities and lack of full adherence to the NIH Revitalization Act should be concerns for all healthcare professionals. These disparities in research participation can lead to an imbalance in the distribution of benefits and opportunities among certain groups, a limited generalizability of scientific findings, and continued trends in health gaps among certain groups [37]. The discussion of whether their exclusion is problematic continues to be controversial.

A number of arguments have been made for the inclusion of women and racial/ethnic minorities in clinical trials. They include, but are not limited to, demographic trends, enforcement of social justice, emphasis on evidence-based practice, and differences in experiences in health conditions.

Although there are clearly many arguments for the inclusion of women and racial/ethnic minority groups in clinical trials, there are reasons given for the exclusion of these groups. Some insist that the potential benefits do not outweigh the drawbacks.

The perceived physical risks associated with injections, needles, and intrusive interventions can impede many from participating in clinical trials. Furthermore, many are concerned that ultimately there will be minimal personal benefits of participation [64]. In a survey of 1,256 research participants, the highest rated barriers involved fear and anxiety. Specifically, the participants feared potential side effects, expense not covered by health insurance, and ineffective treatment or placebo [152]. In a 2007 study, women expressed greater concern about the risks involved in clinical trials than men [65].

One of the prominent images associated with medical research is the research subject becoming a human "guinea pig" [175; 183; 216]. For example, one African American woman who was eligible for a smoking cessation clinical trial study opted not to enroll because she did not want "anyone playing with her mind" [66]. In a 2011 study of African Americans with HIV infection who had participated in a clinical trial, many stated that they were fearful of simply being treated like the subjects in the Tuskegee Study [125]. In another focus group study of Chinese immigrants and service providers, some Chinese immigrants from the community likened clinical trials to "experiments with animals" [67]. In fact, in some languages, the translated word for "clinical trials" is closer to the word "experiment," which unfortunately evokes fear in some patients [68]. This image is also associated with the general belief that certain groups are more vulnerable and more likely to be taken advantage of. In a cross-comparison study with 623 whites, 353 African Americans, and 157 Hispanics, women and racial minorities were more likely to believe that women are taken advantage of in biomedical research [69]. After controlling for socioeconomic status, African Americans were four times more likely and Hispanics were twice as likely as whites to believe that women are taken advantage of in medical research.

Finally, many individuals do not have a full understanding of clinical trials, and this can compound individuals' fears and anxieties. Research indicates that African Americans tend to have less subjective and factual knowledge about clinical trials compared with their white counterparts [184]. Factual or objective knowledge can be measured with questions with a specific answer, while subjective knowledge refers to a person's assessment of their own knowledge. A survey study found that deficits in subjective knowledge tended to predict declining to participate in clinical trials; lack of factual knowledge did not appear to affect participation [184]. In a study conducted in 2006 in an African American community, many participants misunderstood the concept of placebos [70]. Participants in the study conveyed that the use of placebos meant some people would not receive medication. They did not comprehend why the medication or intervention would be denied to patients who needed it for health concerns. This was also reported to be correlated with the atrocities committed in the Tuskegee Study [70].

The way that information is presented to research participants, with the use of technical language and jargon, can impede participation. Use of many unfamiliar technical, legal, and medical terms, for example, can foster anxiety and uncertainty. One study found that the largest barrier to women participating in a clinical trial was how well the study was explained [185]. It is important to remember that medical and legal terms and the many acronyms researchers use in their normal day-to-day professional vocabulary are not part of the language used by laypersons. These "unfriendly" terms end up excluding persons who have not been socialized in the medical profession [71,185]. In a study of 353 breast cancer clinical trial sites, very few offered information in other languages and not all sites offered interpreting services for those with limited English abilities [153]. Minimal supplemental information was provided about the clinical trial. In a qualitative study, the majority of the Latino/a participants argued for materials in Spanish, written in a more reader-friendly manner [154]. For those not proficient in English, use of medical language can be intimidating, which can ultimately create a dichotomy of an "us" and "them" (i.e., researchers and participants) [185].

It is important to note that some terms have cultural connotations. The Spanish word investigaciones, for example, can be misconstrued to mean police investigation in some Hispanic cultures, particularly for those who come from more politically repressive countries [4]. Those who are undocumented may also be concerned enrollment in a clinical trial could trigger investigation of their legal status [217]. Clinical trials and health-related research studies are often conducted at medical centers or academic institutions, which may be more convenient for researchers or sponsors of the research rather than the participants [71]. It is possible that this type of environment reinforces the "doctor culture," which could alienate research participants. Research studies and clinical trials are also based on the notion of medical individualism; however, for many cultural groups, family and social relationships are at the heart of decision-making, including decisions related to health [126]. Furthermore, the logistics and inconveniences associated with traveling to research sites may compound potential participants' fears.

Experiences with negative and discriminatory practices in the healthcare system have bred institutional mistrust, and this can act as a barrier for racial/ethnic minorities participating in clinical trials. The distribution of smallpox-inoculated blankets to Native Americans, the forced relocation of Native Americans to reservations, slavery, medical experimentation on African slaves during the antebellum period, among many other studies, have resulted in mistrust on the part of women and racial/ethnic minorities toward government institutions and, by extension, government-funded research [74]. Fear that information will be withheld from them, general suspicion of the use of control groups, and wariness due to a repeated history of unethical practices continue to be barriers to clinical trial participation [216]. Some have cited the theft of Henrietta Lacks' cells and withholding medical information as events that could recur [218]. In a systematic review of studies of racial and ethnic minority participation in clinical trials, 77% of the studies identified mistrust of the medical establishment and clinical trials [219].

Some cultures adhere to the belief that language can dictate the course of events [83]. For example, in many Asian cultures, talking about illness or death is believed to bring about bad luck [84]. Within this context, it is understandable that some racial and ethnic minorities will be reluctant to participate in health-related research because of the emphasis on illness symptoms and discussion of risks [1,85]. Furthermore, in Western industrialized countries, knowledge acquisition is viewed as a right, but in other cultures, community leaders serve as gatekeepers of knowledge [86].

Cultural differences in gender roles can compound the difficulties women experience participating in scientific research. Having to balance responsibilities of childcare, household-related tasks, and caring for other family members, ethnic minority women are more likely to not prioritize their own healthcare concerns [87]. Depending on the cultural group, assigned gender roles can play a prominent role in whether women will participate in health-related research. For example, due to a patriarchal culture, Korean men assume positions of authority and key decision making, and husbands or other male figures might "forbid" Korean women to participate in health-promoting activities, such as medical research [88].

Western society tends to place emphasis on medical interventions such as vaccinations, immunizations, and antibiotics. In part, this is a reflection of Western biomedical ethos, which is based on individualism and competitiveness [71]. However, many other cultural groups tend to have a more collectivistic and fatalistic orientation, whereby disease and illness are believed to be natural occurrences, not something to fight [71]. For example, some Americans' strong spiritual and religious convictions can impede participating in clinical trials if they adhere to the belief that healing belongs in the hands of God and that they should trust God's plan [216]. Being aggressive in seeking expensive and time-consuming procedures can be perceived as selfish, drawing attention to oneself and not focusing on the family or extended family system [68,71]. This orientation could impede medical research participation.

Cultural beliefs can also affect an individual's view of specific health practices and treatments. When discussing participation in clinical trials that involve drawing blood, some Native Americans express concern that the blood samples would be saved after the individuals die; consequently, the person's soul would be unable to rest [89]. Similarly, some groups view tissue sampling as a violation of the human body, which is sacred and should remain in its natural state [90]. In Chinese culture, some believe that having blood drawn is a sign of disrespect to one's ancestors [92]. Some Asian cultures also believe that drawing or giving blood depletes the life source or life energy, negatively affecting health and vitality [92].

Clinical trials frequently have very specific and rigorous criteria for inclusion in and exclusion from enrollment. This is meant to be an added safety mechanism for research participants, but it can make clinical trials more inaccessible [186]. In addition, if certain exclusion criteria are more common among ethnic/racial minorities, this can lead to under-representation in trials. For example, African Americans often have higher incidences of conditions such as hypertension, heart disease, and diabetes compared to the general population, which can affect participation rates. If clinical trials require research participants to be in excellent health, racial minorities may be disproportionately excluded [130].

Some barriers to clinical trial participation are purely logistical, such as not having access to technology, time, finances, or transportation to get to clinical trials for various tests and follow-up [219]. For example, in a study with Native American Indian college students, one of the barriers cited was distance of the study site [155]. Examining patients enrolled in trials registered between 1993 and 2014 in University of California San Francisco Clinical Trial Management System database, the median one-way trip to the trial location was 25.8 miles [189]. Individuals from low-income areas traveled a median 58.3 miles, compared with just 17.8 miles for patients from higher-income areas. As such, providing transportation to the study site is crucial, if possible [156]. Some individuals will not have telephones or Internet, so research staff will be unable to easily remind them of follow-up appointments [64]. Conflict with job responsibilities and the hours of operation of clinical trials make it difficult for many participants to attend the scheduled appointments [64]. Women's multiple roles may impede participation because they feel they do not have enough time. Lack of childcare is also often cited as a reason for not participating in clinical trials [64].

The principle of respect maintains that all individuals are autonomous and that individuals with limited capacity to make autonomous decisions must be protected [93]. This ethical principle is translated into two practical applications in clinical trials. First, research participants must give informed consent; adequate information about the study must be communicated to participants so they can make an informed decision whether to participate in the study or not. In order to make an informed consent, participants must be able to comprehend the information provided. Researchers and practitioners should keep in mind the following questions:

For adult women of childbearing age, informed consent is based on the expectations that the woman will consider her own interests as well as the fetus's [94].

Informed consent in clinical trials is particularly important because many people mistakenly assume they will be assigned to the experimental or control group based on their own therapeutic needs [61]. In other words, many people believe they will receive treatment tailored to their medical condition if they participate in research [61]. Consequently, the language used on consent forms must be carefully scrutinized. For example, if researchers use the term "treatment" to mean "study procedures" or the term "patients" to mean "research subject," participants might assume that they are receiving certain treatments [61].

In a content analysis of placebo-related information in pamphlets and leaflets given to participants in clinical trials, 84% of the material stated that individuals had a 50% chance of receiving the placebo [131]. Placebo was often defined as a "fake" treatment made to look like the genuine medicine but containing no active ingredient. The pamphlets/leaflets focused on the benefits and risks of the treatment but rarely talked about benefits or risks from the placebo. If informed consent is considered a process (not just a single event), it is important for healthcare providers to continually communicate information about the study, definitions of terms, and possible benefits/risks to potential research subjects.

The second application of respect for persons is voluntary participation. Researchers and practitioners should consider the following questions [95]: Have research participants voluntarily agreed to participate in the study, without influence by any undue pressure or coercion? What is the relationship between the individual who presents the research information and the research participant? For example, do women or immigrants perceive that the healthcare provider is in a more powerful position that could adversely affect their healthcare services if they decide not to participate? Some may feel they will receive substandard services if they do not participate in the study [94]. In addition, the application of the ethical principle of voluntary participation must be placed in a cultural context. As discussed, autonomy, individualism, and self-determination are highly valued in Western societies, especially in the United States. However, in collectivistic societies, it is vital to remember that decision making is group-oriented and the patient may utilize another decision-maker who is accorded authority and respect (paternalism) [96]. Therefore, autonomy will have different connotations in cultures where paternalism is valued [95].

Finally, research participants should be treated with respect, with acknowledgement of their volunteered time and participation. At a minimum, this includes being informed of the findings, maintaining privacy and confidentiality, and having general welfare monitored and protected [220].

Beneficence refers to ensuring that the beneficial outcomes of the study are maximized and the risks are minimized. This includes benefits to the research participant and benefits to the overall knowledge gained for science [97].

Benefits to participation in clinical trials can include [112]:

Risks to participation in clinical trials can include [112]:

Any adverse consequences should be clearly communicated in consent forms. If an adverse incidence does occur, there should be a mechanism in place whereby participants can convey the incident [190].

For women of childbearing age in clinical trials, unbiased information regarding the risks involved both to the individual and the potential fetus should be presented. Any explicit explanations about the responsibility to protect the fetus should be clearly stated in the consent process [98]. Ultimately, providers should review both the benefits and risks to patients and give them time to process the information and make a decision.

As discussed, justice in clinical trials raises the question about who should receive the benefits and who should bear the burden of research [93]. It is important to ask who would benefit from the study—the research participants, the researchers, the sponsoring agencies/organizations, or those who have the medical condition [99]. It is also important to assess which groups will have an opportunity to access clinical trials and if any groups risk being marginalized [191]. If the study benefits everyone except the research participants, is that acceptable? What if a medication is too expensive for the participants to easily access after the experimental research is completed, or if the side effects of the intervention are painful [99]? Ultimately, injustice results in inequities, or the unfair distribution of benefits and burdens/risks due to structural factors [221]. These questions must be evaluated in order to adhere to the ethical principle of justice.

The term "hard-to-reach populations" has been used to categorize certain groups who are not easily accessed or served due to cultural, economic, and geographic factors. While some groups may be difficult to access, such as those in rural or frontier areas, others just may not have been the subject of outreach on the part of researchers [88]. There are several basic guidelines that might be helpful in recruiting women and racial/ethnic minorities to medical research. The first is having knowledge of the lifestyles of the group being targeted. Experts have emphasized the need for researches to understand the unique cultural and social practices of the group being targeted [88]. For example, when recruiting women to participate in a clinical trial, it may be important to offer evening and weekend hours in order to accommodate childcare needs, household responsibilities, and work schedules.

As noted, clinical trials and health-related research studies frequently take place at medical centers or academic institutions [71]. While these locations may be convenient to the researchers or sponsors, they may not be convenient to participants who are unfamiliar with the area or the local transportation system. The environment may be foreign and could potentially breed institutional distrust [71]. Healthcare professionals can play a vital role in mediating this perceived gap by facilitating access to clinical trials and resources and developing rapport with potential participants so they feel involved in the research process [64]. For example, in a study of Korean immigrants, study sites were located in areas where Korean Americans and immigrants frequented, such as ethnic grocery stores [88].

Word-of-mouth from individuals who are perceived to be trustworthy has been found to be the most effective recruiting method in under-represented groups [100,101]. In a cancer screening study targeted to older Filipino women, personal invitations from people whom the potential participants knew were a crucial factor in decisions to take part in the study [100]. This phenomenon was replicated in recruiting and retaining Hispanic research participants for a longitudinal study [101]. Initially, the researcher mailed flyers and conducted community presentations, but these efforts did not result in enrollment. However, when a community representative approached individuals one-on-one, enrollment increased. Some experts recommend message-mapping to ensure that communication to potential participants are evidence-based, intentional, systematic, and clear, using a variety of communication mechanisms [222]. Scripts are written and analyzed for clarity and comprehension. Key messages, with three to five supporting points, should be clearly communicated.

Collectivistic groups are more likely to value the process of relationship building, and this can be a key part of research outreach. In a study exploring differences in interactions of black and white patients with oncologists, black patients' interactions were briefer than their white counterparts [157]. There were also fewer mentions of clinical trials and less discussion about the nature of the various clinical trials offered. In a study that targeted Hispanic women for a dental disease prevention study, the cultural value of personalismo (or personal contact) was emphasized [102]. Direct, personal contact is beneficial for Latino/a participants because this type of communication reinforces cultural values regarding the importance of developing relationships that promote trust (confianza) and respect (respeto) ensue.

Maintaining frequent contact, actively listening to the women's stories, and sending birthday cards and handwritten, personalized messages helped participants to feel they were important, not simply trial subjects. In a study examining an intervention for African American female breast cancer survivors, researchers worked with African American churches to improve recruitment. Letters were written by church leaders linking African American women's faith, spirituality, and the intervention study as a ministry [132]. Because of African American culture's strong emphasis on spirituality and religion and integrating spiritual and religious dimensions to day-to-day life, invitation letters framed African American breast cancer survivors' participation as a way of helping others.

Healthcare providers can help communities regain trust in research by fostering and facilitating communication, consultation, collaboration, and partnerships in order to build public and community trust [158]. When COVID-19 became highly politicized, the importance of collaborating with a host of systems was highlighted to alleviate anxieties about the COVID-19 vaccine trial [223]. Messages and activities that represent trusted voices to the community should be coordinated. Therefore, strategies to develop collaborations with communities and leaders are key in recruiting women and racial/ethnic minorities into clinical trials [156,192]. In some cases, gatekeepers maintain a strong presence in communities, particularly in some ethnic minority communities. In the Korean immigrant community, pastors, business owners, leaders from ethnic organizations, ethnic media outlets, physicians, service providers and advocacy organizations, and religious leaders can act as a conduit for research. Some may be more receptive to clinical trials, while others view research activities with more caution [88]. Developing partnerships with physicians and medical professional associations is also important [223]. In a focus group with Chinese participants, they mentioned that one motivating factor to participating in a clinical trial is a recommendation from their physician [159]. Consequently, it may be helpful for research team members to create a community asset map [88]. This involves highlighting specific resources within the targeted community and discovering the variety of individuals, organizations, social clubs, and businesses that would be helpful in recruiting research participants [223]. Additional word-of-mouth referrals or recommendations from the initial compilation of resources may be added to the profile. A continual examination of this map, including an assessment of any new cultural, social, and political forces that may have an impact, is highly recommended [88].

In a systematic review of previous clinical trials studies published with a focus on recruiting racial and ethnic minorities, community partnerships were effective in recruiting racial and ethnic minorities for clinical trials in 68% of the cases [133]. The retention rate was 65% for studies that mentioned data about retention. Individuals who have participated in clinical trials can also serve as recruitment partners, provide feedback on study design and consent forms, and present trial results to lay audiences [193].

Creative research partnerships should also be considered. Instead of one-sided research, collaborative projects, with creative or educational results, can be effective. For example, in one such project researchers forged a partnership with an African American sorority to recruit African American women for a genetics study [103]. The goal of this partnership was to educate African American women about the hereditary component of breast cancer and to increase African American enrollment in the national Cancer Genetics Network [103]. Although the partnership yielded very modest enrollment, the authors were confident that the lessons learned could lay the platform to building and improving future partnerships with other sororities. For example, they learned that rapid communication was crucial, as many volunteer organizations have competing interests [103].

Post-project engagement is just as important as pre-study planning [194]. Ideally, community partners could also help analyze and interpret the findings [192]. In a 2012 meta-analysis, community partners were discussed in the articles as assisting the researchers in interpreting the findings only 21% of the time [133]. However, community partners were involved in helping to develop the interventions more than 90% of the time. Partners may be less interested in the analysis phase due to perceived necessity for specialized skills, but this underscores the importance of engaging in a dialogue to help identify each parties' strengths and interests when it comes to the level of involvement.

The staffing of a research team should include a community representative [104,192]. This individual would serve as an advocate and a facilitator for the community, bringing concerns, questions, and issues back to the research team. They could also serve as cultural consultants, which are also key to the success of researchers who desire to penetrate "hard-to-reach" communities. For example, consultants are often needed in research with Native Americans because there are specific processes that must be negotiated with tribal entities [104]. Lack of cultural competency and sensitivity of staff members has been identified as a barrier to clinical trial participation [222]. Clinical trial coordinators are the face of the study, and they implement a host of invisible "back office" activities to help recruit research participants. Being sensitive to cultural and logistical barriers can help make potential participants feel connected and appreciated.

In another study recruiting elderly African American women for cancer prevention control studies, researchers found that study helpers, local spokespersons, and familiar authority figures can legitimize the study and assist in improving recruitment [105]. Study helpers were local African American residents who accompanied the researchers conducting door-to-door canvassing. Doors were more likely to be opened when people saw familiar African American women from their own community [105].

Faith communities and churches can also powerful influencers with certain racial and ethnic minority groups. For example, the Dose of Hope program, designed to close gaps in health care utilization, relied on churches to disseminate the message of clinical trials to older African Americans [158]. Other community settings (e.g., barbershops, beauty salons) and events (e.g., health fairs, barbeques) can also be effective venues for recruitment [179].

Marketing strategies are also equally important. Community partners can be involved in all steps of marketing, including logo development, selection of media outlets, and targeted language [134]. Many assume community outreach and other racially and ethnically targeted marketing methods are more expensive and less effective, but this is not necessarily true. In a study of the effectiveness of smoking cessation outreach to African Americans, researchers found that the cost per research participant was $27 when using the community outreach method, $120 for advertisements on billboards, $940 employing ads on mass transportation systems, and $1,208 using newspaper ads [135]. They are also effective in achieving the desired outcomes of recruitment. One example of this method was the inclusion of an "Asian" themed greeting card along with the traditional marketing packet about the study; in this case, the researchers were specifically seeking Asian participants [224]. Those who received the greeting card were 4.5 times more likely to enroll in the study compared with those who received only the traditional marketing materials.

Creating and promoting awareness about the overall value of clinical research is also important [106]. Community education should not simply be about telling people that clinical research is good for them [43]. Rather, it is more important to ask and listen to what the community values and needs. Furthermore, education regarding the various aspects involved in clinical trials, the logistics, and the processes is needed.

In regards to educational material, the consensus is that all instructions, brochures, flyers, and videos be culturally and linguistically appropriate. Culturally appropriate logos, images, and colors are important as is informational content that is appropriately translated to the targeted group. Brochures, face-to-face presentations, and educational materials about the condition or intervention being studied should be conveyed in a culturally sensitive manner. Written materials may not be the best option for educational outreach. For example, researchers in one study disseminated a video to Hispanic women to reduce language barriers [104]. Creative approaches, such as videos, multimedia, and photos/images, may also be used to explain clinical trials [195]. When appropriate, information may be presented on social media platforms [194]. Instead of relying only on text, these approaches could facilitate greater comprehension of the study and higher retention levels [195]. In terms of directly speaking to women's participation, informational components may address the importance of women's participation in research to benefit not only an individual's health but the larger collective unit as a whole [106,136].

Nurses, social workers, and other practitioners play key roles in educating patients and advocating for clinical trials [196,197]. They can initiate conversations and answer questions, and they may also serve as liaisons between members of the research team and other healthcare providers [197]. Education for research staff regarding potential barriers to participation for women and racial/ethnic minorities may be helpful [192]. One study found that research site coordinators and research nurses held perceptions that minorities, and to a lesser extent women, were less likely to enroll in clinical trials because they were less interested in participation [107]. The research workers indicated their most effective interactions were with white men. They also stated they were less likely to enroll an individual who had missed previous appointments or did not speak English. Although it is true that racial and ethnic minorities are less likely to enroll in clinical trials, these views can ultimately affect recruitment decisions [107].

Assisting women and racial/ethnic minorities from their stated intention to participate to the actual execution of the decision involves addressing the practicalities and logistics of fitting the participation into day-to-day responsibilities [106]. As discussed, traveling to the research sites on multiple occasions for testing can be a burden, infringing upon research participants' time and finances. Furthermore, childcare is often a logistical barrier to participation, particularly for women. Social workers, nurses, and case managers can advocate for resources to deal with these logistical dilemmas and assist participants to coordinate necessary services, as convenience is key for enhanced research participation [52,64,219]. In some trials, childcare and transportation are provided to help with recruitment and retention of women research participants [134]. In another study of nutritional guidance for low-income mothers, participants were scheduled for follow-up interviews during times when they were already in the medical clinics for scheduled well-baby visits [137].

Compensation for the time spent traveling and engaging in study participation should be carefully considered [106,188]. In one study, a several-phase incentive plan was designed to provide grocery gift cards in stages with gradual increasing amounts [137]. In addition, being culturally sensitive to the form of incentive is also important. In one study conducted in the Khmer community, community informants advised that monetary incentives in the form of checks may not be culturally appropriate because many of the targeted research participants worked primarily for cash [108]. In this case, grocery coupons were identified as more culturally sensitive compensation. At the same time, checks, grocery redemption cards, and any other incentive compensation that requires identification documentation for redemption may not be culturally sensitive, particularly for groups who are concerned about their immigration status [138]. Cash may be optimal, but if the funding agency of the study requires participants' social security numbers for tax purposes, this could be viewed as an impediment for some participants [138].

Informed consent is a vital aspect of the healthcare system and of scientific research. While some immigrants may be reasonably fluent in English for day-to-day activities, they may be less comfortable communicating in English about healthcare issues [95]. Some individuals may sign a consent form without fully understanding the significance due to cultural belief systems about the role of authority figures. For example, a study of Japanese elderly research participants found that 40% had signed the consent form because they simply respected their physicians' authority and deferred to their decision making [83]. Furthermore, they perceived that not signing the form would be disrespectful. Given that loss of respect is a cultural value important to some immigrants, researchers should reiterate to research participants that a signature on the consent form is not binding [94]. In the United States, an individual signs the consent form, signifying he/she understands the information provided to him/her. However, in other cultures, community consent and decision making are advocated [149]. In patriarchal or male-dominated cultures, the male head (e.g., husband) may be the one to give consent for a female research participant [225]. Research that involves Native American Indian tribal groups or indigenous groups, the community leader, elders, grandparents, and/or other relatives provide consent (not the individual) [149].

It is incumbent upon the healthcare or behavior health professional to assess if the research participant has full understanding of the study and to encourage him or her to repeat the information on the form [94]. In a qualitative study that explored oncologists' communication styles and interactions with patients regarding cancer clinical trials, their role as educator was highlighted. Because the information is often complex and daunting, the oncologists spent time with their patients talking about the technical aspects of the clinical trial, side effects, and randomization [91]. In some cases, traditional written consent forms may need to be replaced with oral, video, audio, or even pictorial methods [225]. Thumbprints may also be permissible in lieu of the signature. Patient navigators, if available, can be beneficial in helping participants navigate through the healthcare system [224]. If there are language barriers, interpreters may be necessary. Having a diverse research team, including members who are proficient with the targeted study population's language, can also help overcome language and cultural barriers and assist with engagement and alleviating fears [186].