Screening results
A total of 1861 results were returned from the search and screened for inclusion. Overall, 72 articles were included within this review (see Fig. 1 for screening data). The majority of the included articles (74%) were from the USA and a third focused on cancer trials (33%). In relation to the type of under-served groups included, half of all articles (50%) focused on inclusion issues relating to ethnic minority populations. The remainder focused on general under-served groups, children and young people, adolescents, women, and others (e.g. deaf, transgender). Sixty-one (85%—see Additional File 1 for more details) of the included articles reported on strategies to improve inclusion (of which n = 13 also included information on barriers). Eleven articles reported on barriers to inclusion alone. The 72 papers are included within the “Results” section, Additional File 1, or a combination of these.
Barriers to inclusion
A consistent theme across the literature is that many of the barriers relating to inclusion are the same as those that impact trial design and delivery [13]. The nuance is around how these barriers present among different, under-served groups, which is often unique to each population’s particular circumstances, background, beliefs, and needs. Barriers are summarised below.
Language and communication
This well-known barrier to inclusion, particularly among recent migrant ethnic groups, remains an ongoing issue. In trials conducted in the USA and Europe, being unable to speak and/or read English is a common barrier faced by individuals [14]. Closely related to this is the ability to speak and/or read English to a certain level, without fully comprehending the meaning of everything that is said or written [15]. There is also the further issue of how this decision is made, i.e. who decides whether someone speaks good enough English to take part and what criteria are used. Importantly, language barriers can also be viewed as a failure to show respect to potential participants if the information has not been made available in a culturally relevant and accessible language format [16].
Finally, language/literacy barriers do not only apply to migrant ethnic groups, as other under-served populations also experience language/literacy barriers due to a range of issues such as disability or the impact of lack of education/access to education on literacy. For example, deaf individuals may need support with sign language [17, 18].
Poor communication was another common barrier that was predominantly identified in studies with groups [19, 20]. This may relate to literacy generally and also to health literacy more specifically [15]. Similarly, studies in children need age-appropriate communication [21].
Lack of trust
For potential participants, having a lack of trust in research, doctors, investigators, drugs, and the medical industry was a recurring theme across the literature [14,15,16, 19, 20, 22,23,24]. This may arise from previous bad experiences and previous severe adverse events in reported studies [25] and was often compounded by related beliefs or fears [23]. For example, older adults may fear that experimentation could damage their health [26] or that participation would not benefit younger generations [27].
Access to trials
A lack of access to relevant clinical trials manifested in a number of different ways. First, a lack of information about trials for which potential participants are eligible and available is a barrier [22, 23, 28]. This may particularly be the case for people without a usual place for care, who are also often not eligible for relevant trials [29]. Similarly, the inability to access the healthcare or research centre was a barrier [20, 28, 30]. Not being invited to eligible trials was another access-related barrier [31]. Finally, other practical factors preventing access to trials more generally remain important in under-served groups, such as recruitment competition for other studies and lack of recruitment staff [32].
Eligibility criteria
Some studies highlighted that inclusion/exclusion criteria often disproportionately exclude people in under-served groups, including older adults, pregnant women, obese individuals, people with existing/multiple chronic conditions (multi-morbidity), and people with severe mental illness [27, 28, 32]. This exclusion may be explicit; for example, lack of capacity to consent is a common exclusion criterion that means individuals without this capacity are denied the opportunity to participate in research [33]. It also means there is consequently a limited evidence base regarding health interventions in this population [33]. On the other hand, eligibility criteria may indirectly exclude some populations to a greater extent than others; for example, exclusion criterion may be more prevalent in some ethnic minority groups than in White Europeans, such as chronic diseases [34].
Attitudes and beliefs
This barrier can present in many different ways and is often context and populationspecific. Examples that arise in the literature include no personal or family history of the condition under study [29]; stigma surrounding the condition under study [13, 16, 24]; beliefs among older adults that they were too old to participate in trials [26]; concerns around immigration status for some ethnic minority populations [23]; concerns about side effects or taking an experimental medicine [27, 35]; stress, fatalism, and a conservative attitude to risk-taking among Asian women [25]; religious beliefs [30]; “Guinea pig” perceptions [36]; not feeling comfortable, welcome, or respected [36]; privacy concerns [23]; and negative attitudes to clinical trials [30]. In addition, not only the individual’s own beliefs and attitudes, but also those of their friends and families can prevent under-served groups from taking part in trials, as lack of social approval was found to be an important barrier [27, 28, 36, 37].
Lack of knowledge around clinical trials
There were a large number of studies that identified a lack of understanding about clinical trials as a barrier in a range of populations, particularly among ethnic minorities [14, 19, 22, 30]. Examples of where this lack of knowledge/information was apparent included the trial process such as during recruitment or the collection of data [22, 23].
Logistical and practical issues
Logistical and practical barriers were particularly prevalent among under-served groups studied [15], including lack of transport [16, 20, 28, 30, 32], time [16, 22, 24, 28], additional visits/tests [25], indirect costs associated with participating [23], childcare [20, 30], work responsibilities [20], and issues related to the condition under study, e.g. pregnancy or drug abstinence [24, 25, 28].
Other barriers
Aside from these key barriers that were commonly referred to across the literature, single papers also highlighted the following barriers which may be relevant to clinical trials, including lack of follow-up during the recruitment process [32], lack of investigator/study team outreach to communities [28], challenging patient social and structural factors (e.g. homelessness) [24], difficulty locating eligible patients in clinic (HIV-related study) [24], and unavailability of research staff out-of-hours [35].
Evidence-based strategies and enablers
The main evidence-based strategies and enablers to improving inclusion identified through the literature search are fully detailed in Additional File 1. The remainder of this section summarises the key evidence-based strategies identified within the literature.
Cultural competency training
There was a range of evidence suggesting that inclusion in trials was improved when staff had received specific training on that topic [13, 15, 19, 38,39,40,41,42,43,44,45,46]. This may include teaching study staff about cultural humility, existing health inequities, and the background and context as to how these have arisen [44], including previous research abuses (e.g. deception and mistreatment in research, such as the Tuskegee syphilis study). Acknowledgement of these was found to be important, particularly for African Americans [47]. It was also noted that applying knowledge of culturally important practices was also beneficial [16, 42, 48].
Community partnerships
A recurring theme was that strategies that closed the gap between the study team and the community were very effective [17, 19, 20, 38, 42, 46, 49,50,51,52,53], particularly community-based participatory research (CBPR) approaches [54, 55]. Some specific strategies around this included the use of a community advisory board [38, 46]; patient advocates/navigators, including to recruit participants [38, 49, 56]; ongoing partnerships with community members, leaders, groups, and organisations [19, 20, 38, 41, 42, 49, 50, 52, 56, 57]; direct outreach to community participants followed by electronic health record data for clinical information and follow-up [58]; oversight by a community panel [20]; and consultation with community members regarding study resources [49].
Personalised approach
Emphasis has been placed on strategies that lead to a more personal approach within clinical trials. These strategies may help people feel that they are seen both as an individual, as well as part of the groups with which they identify. Examples include building good rapport and relationships with participants [48, 51, 59, 60], individual communication styles [60], a human (i.e. not automated) phone call in the participant’s preferred language [61], birthday and holiday cards [57], thank you letters [53, 57], acknowledgement certificates [53], and relationship-centred recruitment and retention [43].
Multilingual materials and staff
A number of studies directly overcame language barriers for non-English speakers by providing bilingual staff [20, 42, 47, 52, 57, 59, 62], materials in non-English languages [20, 42, 49, 57, 62, 63], and/or an interpreter [42, 63]. Similarly, in a study conducted with deaf individuals, a variety of contact methods (video call and email) and materials in both sign language video and written English were found to help [17]. Many studies explicitly aimed to recruit study staff from under-served groups so that research teams are representative of the people being recruited, especially if from the local community [13, 17, 39, 47,48,49,50, 52], and some even matched study team members and participants on ethnicity [54].
Communication-specific strategies
Aside from language, a number of other strategies specifically related to communication have been implemented, including community providers or physicians sending letters of support to potential participants prior to study contact [42, 49, 62], mass mailing [64, 65], third party contact obtained at enrollment [59], out-of-hours contact [52, 59], keeping phone calls short [59], reminder calls or postcards [57, 59], regular study updates [57], maintaining up-to-date information [59], using social media for recruitment and retention (particularly Facebook) [56, 66], appropriate readability/simplified English materials [20, 44, 47], patient-centred/preferred communication methods [20], use of multimedia [15, 30], and appointment cancellations followed up vigorously [67].
Increasing understanding and trust
In order to tackle barriers related to a lack of understanding or trust in clinical trials, several studies provided educational sessions for communities [23, 39, 47, 49, 50, 65, 68], with one successfully employing teach/teach-back methodology [20]. Others aimed to build trust through communications [50] or by sharing patient safety information [47]. Using social proof was also a key strategy for improving trust either through participant testimonials [56, 63] or friends and family referrals [30, 64, 69].
Tackling logistical barriers
Multiple logistical barriers to recruitment and retention exist in clinical trials, and they remain a pertinent issue in under-served groups. Strategies that attempt to overcome these include flexible timings and locations of study visits [16, 20, 70], including home-based assessments [48]; providing childcare [42]; transport [24, 42]; and reducing costs associated with trial participation [42].
Additional strategies
Aside from these key strategies that were commonly referred to across the literature, some articles also highlighted the following enabling practices which may be relevant to clinical trials, including leadership from organisations and management around inclusion [38, 40, 42]; partnering with local healthcare centres/practices and clinical staff [20, 35, 43, 44, 49, 67, 71]; non-discriminatory inclusion/exclusion criteria [35, 48, 53, 64, 72]; recruitment targets for diverse groups [48, 52, 53, 64, 72]; electronic database to track participants throughout the study [44]; two-step method of collecting sex at birth and gender identity on data collection forms [46]; alleviating burdensome data collection [73]; study-branded items with study information, e.g. fridge magnets [53, 59]; and family involvement [42, 48].
