This study is the largest and first population-based study in the UK regarding COVID-19 vaccination and vaccination trial perceptions. Our results show that less than half of respondents (41.4%) are interested in partaking in vaccination trials. Interestingly, the UK COVID-19 vaccine registry shows that only 357,706 participants have registered as of the 1st December, which is estimated to be only 0.5% of the UK population [13], [14]. Furthermore, only 6 out of 1518 UK COVID-19 studies were collecting data on ethnicity.
Interestingly, this is the first study to identify that ‘other cities’, smaller cities, such as Leicester and Aberdeen are more likely to participate in trials compared to larger metropolitan ‘core cities’, such as London and Birmingham. A reason for this could be attributed to ‘core cities’ having greater pockets of inner-city poverty and health inequalities, compared to ‘outer cities’ [15].
The BAME community are less likely to get involved in the COVID-19 vaccination trials, despite them being at higher risk of COVID-19. This correlates with our study results. The UK COVID-19 vaccine registry also demonstrates that BAME groups are short of reaching national targets representing less than 8% of the registry despite representing 13% of the population [13]. Of note, the Black population only consisted of 0.5% of the total number. Trials have historically struggled with gaining a diverse population with greater intervention required to engage ethnic minority groups into trials [16]. In US studies, the Black population have been significantly under-represented in clinical trials [17]. The under-representation of, the Black community in particular, is likely to be attributed to mistrust in the medical profession, as well as historical oppression and health inequalities [18], [19]. A recent study found that only 14% of Black adults trust that a vaccine would be safe and fewer than half of Black adults would accept a licensed COVID-19 vaccine even if freely available [20].
Our findings suggest that mistrust is a key factor in non-uptake for vaccination trials. Free text comments from the survey revolved around the idea of the BAME community being used as ‘guinea pigs’ for trials to verify vaccine results, and mistrust around government strategies. Similar sentiments have been found in US studies [17], [20], [21]. This was likely to have taken influence from social media views at the time of survey completion, particularly those highlighting adverse events from vaccine trials and vaccines trials being rushed. Furthermore, there are greater anti-vaccination sentiments shared on social media and are spread quicker compared to positive ones promoting trial uptake [22]. Multiple studies have highlighted a number of other reasons as to why trials tend to disadvantage minorities from attending. This includes; poor health literacy, hidden costs related to reaching trials, lack of knowledge about the condition being studied, distrust in the research process and the researchers, and language barriers [8], [23].
Whilst the highest proportion of BAME respondents were in cities, there seems to be even less interest from the BAME community in ‘core cities’ compared to ‘other cities’. There is a greater proportion of the BAME community residing in the inner city groups of large cities and these areas tend to have poorer health outcomes and suffer greater health inequalities [24], [25]. Whereas BAME groups in smaller cities are, however, more likely to consider partaking in trials as these areas are likely to be less economically deprived and tend to have more educated BAME groups [25].
In our study, the over 70 s group were the least willing to partake in vaccination trials. For the vaccine registry, as of November 2020, over 80 s consist of only 1% of COVID-19 vaccination trial participants [13]. This is despite providing much needed diversity and clinical benefit compared to younger and healthier participants. Although the increased risk of morbidity and poly-pharmacy brings unique challenges of how effective the vaccine could be, participation from the elderly can render the trials more generalisable. Unfortunately, elderly patients tend to have greater refusal rates than the younger population and many do not actively seek out clinical trials or are even informed of the availability of clinical trials [8].
There are multiple reasons as to why the elderly hesitate to participate in clinical trials. Many within the elderly population do not understand the possible benefits of the research being undertaken. Informed consent in the elderly can also be complicated by the possibility of cognitive impairment. Transportation difficulties is consistently cited as a primary concern and a barrier for elderly adults considering participation in a research study whilst mobility issues could also potentially make follow-up visits difficult [8].
In our study, the majority of those over 60 s who were not interested in participating in trials were from ‘small towns’ and ‘villages’, which are known as more rural areas. Participation in clinical trials in rural areas are significantly lower [26], [27]. Often these areas have a greater older population and are further away from trial sites, making it harder to access. Furthermore, rural participants are likely to be less aware about vaccine trials and have more misperceptions than inner city participants [21].
The perception of COVID-19 vaccine can play a key role in deciding whether an individual will partake in a vaccine trial. Our results showed that the 40–59 age group have the greatest interest in participating in vaccination trials. There is also interest from those who had no heath conditions. These younger and healthier adults may be motivated by altruism and may see the societal benefits of vaccine research, surpassing any personal health risks [28], [29]. Our study found that if one was interested in partaking in the vaccination trial, then they are also likely to have a positive perception of the COVID-19 vaccine on overall health and of the vaccine trials. Furthermore, they are more likely to agree on the importance of having a variety of people, of all backgrounds, to participate in vaccine trials.
Despite the majority of our respondents being female, younger males were more interested in partaking in vaccine trials. Historically women, particularly of child bearing age, are harder to recruit for vaccination trials [30]. Studies have shown that females, particularly those with underlying health issues, can also have more distrust in pharmaceutical companies and have been previously under represented in other respiratory trials [10].
Future Challenges
The challenges with recruitment for trials are set to increase, as phase 3 vaccine trials continue to take place from 2021 [31]. Barriers will become more pronounced when recruiting to placebo phase three trials and further non-inferiority studies, where vaccines will go head to head. Thus, there is a need to consider the redesign and reshaping of these studies to consider these barriers, and engage the patients in the recruitment plan for these newly designed studies.
Vulnerable groups, such as the BAME and elderly, are most likely to receive an approved vaccine first so would be hesitant to partake in non-approved vaccine trials. It may also be considered unethical to have these high-risk groups involved in testing once there is already an approved vaccine. In terms of the young population, they may well be one of the last groups to receive an approved vaccine, and so may be more drawn towards involvement in trials.
The UK will also be the first country to do human Challenge trials with COVID-19 in 2021 [32]. The challenge trial will involve infecting healthy participants with the COVID-19 virus in a controlled environment and then being administered the vaccine [33]. Eligible participants must not have any previous health conditions so that they experience only a mild infection [29], [32]. Consequently, high risk groups such as the elderly are likely to be excluded from these trials [29].
Whilst our study shows willingness from those who have no health conditions, more work still needs to be done in recruiting high numbers of healthy young participants to adequately power these Challenge trials. In our study, the odds ratio for those under 40 was less than 1, suggesting that there is a large proportion of young people who are disinterested in participating in trials. This is somewhat surprising, as previous studies showed a high willingness (64%) towards vaccination trials, particularly in university students [28]. More worrying, any adverse events with these challenge trials are vulnerable to negatively tipping the balance in vaccine uptake rates.
Tackling barriers towards trial recruitment
This study has shown that there is a clear need for launching national awareness and education campaigns. The aim would be to improve the public’s knowledge about the burden of diseases and the need for vaccine development, thereby harnessing the public’s motivation to take part [34]. Moreover, campaigns will need to tackle issues of mistrust whilst remaining cautious with economic coercion that would aim to drive participation in the economically marginalised [28].
There may be a need to bring the trial to the subject where distance is a barrier. Mobile units could be formed to conduct study visits remotely. This would eliminate the need for the subject to find transport to the clinical trial site and reduce travel time, therefore reducing the impact on the subject’s daily commitment [34]. Alternatively, the use of telemedicine approaches has become progressively more popular and acceptable by health authorities, medical doctors and patients after the current pandemic [35].
Researchers should remain flexible in their approach and incorporate different types of media and community resources to enhance recruitment. Community engagement techniques are being increasingly used by the NIHR, such as the INCLUDE initiative. This initiative has been formed to ensure there is adequate representation of under-served groups, which will be done through careful funding and regulatory approval [36]. Informed consent for participation in a clinical trial should be kept simple and short to ensure adequate understanding of the subject, yet comprehensive to ensure useful information can be collected while preserving ethical principles of informed consent [8]. Consent should be made possible to be done in various languages. Other solutions can involve having more minority researchers conducting the trials. Having greater diversity in principal investigators can be beneficial with this. This may curtail bias in recruitment of participants from underrepresented populations and allow for improved communication during recruitment [17], [20], [23].
It is important to engage General Practitioners (GP) into vaccine trial recruitment, where they can act as key facilitators for older patients and BAME involvement in trials [8], [20], [21]. Not only can GPs offer a more personalised approach, but they can also facilitate in building greater awareness, as often the barrier is a lack of awareness of trials [8]. However, a barrier to this can be a lack of confidence in GPs being able to recruit trial participants. This can be overcome by establishing formal training for GPs on discussing clinical trials with patients and with specific patient populations to facilitate improved shared decision-making [17].