Randomised trials of COVID-19 vaccines in Africa – charting the path forward

Vaccine clinical trials should strive to recruit a racially, socioeconomically, and ethnically diverse range of participants to ensure appropriate representation that matches population characteristics. Yet, full inclusion in research is often limited. A single-center retrospective study was conducted of adults enrolled at Brigham and Women's Hospital (Boston, MA) between July 2020 and December 2021. Demographic characteristics, including age, race, ethnicity, ZIP code, and sex assigned at birth, were analyzed from both HIV and COVID-19 vaccine trials during the study period, acknowledging the limitations to representation under these parameters. We compared the educational attainment of vaccine trial participants to residents of the Massachusetts metropolitan area, geocoded participants' addresses to their census block group, and linked them to reported median household income levels from publicly available data for 2020. Frequency and quartile analyses were carried out, and spatial analyses were performed using ArcGIS Online web-based mapping software (Esri). A total of 1030 participants from four COVID-19 vaccine trials (n = 916 participants) and six HIV vaccine trials (n = 114 participants) were included in the analysis. The median age was 49 years (IQR 33-63) and 28 years (IQR 24-34) for the COVID-19 and HIV vaccine trials, respectively. Participants identifying as White were the majority group represented for both the COVID-19 (n = 598, 65.3%) and HIV vaccine trials (n = 83, 72.8%). Fewer than 25% of participants identified as Hispanic or Latin. Based on ZIP code of residence, the median household income for COVID-19 vaccine clinical trial participants (n = 846) was 102,088 USD (IQR = 81,442-126,094). For HIV vaccine clinical trial participants (n = 109), the median household income was 101,266 USD (IQR 75,052-108,832). We described the characteristics of participants enrolled for HIV and COVID-19 vaccine trials at a single center and found similitude in geographical distribution, median incomes, and proportion of underrepresented individuals between the two types of vaccine candidate trials. Further outreach efforts are needed to ensure the inclusion of individuals from lower educational and socioeconomic brackets. In addition, continued and sustained efforts are necessary to ensure inclusion of individuals from diverse racial and ethnic backgrounds.

Prioritizing incarcerated populations for COVID-19 vaccination and vaccine trials

Black and Latino individuals are underrepresented in COVID-19 treatment and vaccine clinical trials, calling for an examination of factors that may predict willingness to participate in trials. We administered the Common Survey 2.0 developed by the Community Engagement Alliance (CEAL) Against COVID-19 Disparities to 600 Black and Latino adults in Baltimore City, Prince George's County, Maryland, Montgomery County, Maryland, and Washington, DC, between October and December 2021. We examined the relationship between awareness of clinical trials, social determinants of health challenges, trust in COVID-19 clinical trial information sources, and willingness to participate in COVID-19 treatment and vaccine trials using multinomial regression analysis. Approximately half of Black and Latino respondents were unwilling to participate in COVID-19 treatment or vaccine clinical trials. Results showed that increased trust in COVID-19 clinical trial information sources and trial awareness were associated with greater willingness to participate in COVID-19 treatment and vaccine trials among Black and Latino individuals. For Latino respondents, having recently experienced more challenges related to social determinants of health was associated with a decreased likelihood of willingness to participate in COVID-19 vaccine trials. The willingness of Black and Latino adults to participate in COVID-19 treatment and vaccine clinical trials is influenced by trial awareness and trust in trial information sources. Ensuring the inclusion of these communities in clinical trials will require approaches that build greater awareness and trust.

Pregnant and lactating mothers have historically been excluded from clinical trials. To understand the shift from excluding to including this population in COVID-19 vaccine trials, we conducted a review of guidance issued by countries in southern Africa over the last three years. We conducted a review of documents and official statements recorded on Ministries of Health websites, and social media platforms, the World Health Organisation website, the COVID-19 Maternal Immunisation tracker and the African Union official webpage. Search terms included COVID-19 vaccination policies, guidelines for pregnant and lactating women, COVID-19 vaccination trials and pregnant women. We retrieved and reviewed policies, guidelines, and official statements from 12 countries. We found inconsistencies and incomplete guidance in respect to the inclusion of pregnant and lactating mothers in COVID-19 vaccine trials from the selected countries. Of the twelve countries reviewed, Namibia and South Africa had clear guidance on vaccination plans and implementation for pregnant women, and their inclusion in COVID-19 vaccine trials. Explicit and clear guidelines are critical in communicating changes in policy towards those deemed vulnerable for them to participate in vaccine trials. This review provides lessons for future pandemics on managing changes in guidance towards those groups historically excluded from vaccine and clinical trials.

Toward an observatory of the evolution of clinical trials through phylomemy reconstruction: the COVID-19 vaccines example

BackgroundHealth care workers (HCWs) are among the high-risk groups in contracting and dying from COVID-19. World Health Organization estimates that over 10,000 HCWs in Africa have been infected with COVID-19 making it a significant occupational health hazard to HCWs. In Ghana, over 100 HCWs have already been infected and dozen others died from the virus. Acceptability and uptake of the COVID-19 vaccine is therefore critical to promote health and safety of HCWs as the country battles out of a third wave of the pandemic.ObjectiveThe study sought to ascertain the correlates of HCWs likelihood of participating in a COVID-19 vaccine trial and accepting the vaccine when given the opportunity.MethodsThe study was a web-based cross-sectional survey among HCWs (n = 1605) in all sixteen (16) administrative regions in Ghana. Data were analyzed with STATA statistical analysis software (version 14). Chi-square (X2) and Fisher’s exact tests were used to test for differences in categorical variables; bivariate probit regression analysis with Average Marginal Effect (AME) was employed to ascertain the determinants of HCWs’ likelihood of participating in a COVID-19 vaccine trial and taking the vaccine.ResultsIt was found that 48% of HCWs will participate in a COVID-19 vaccine trial when given the opportunity; 70% will accept the COVID-19 vaccine; younger HCWs (AME = 0.28, SE = 0.16, p < 0.1), non-Christians (AME = 21, SE = 0.09, p < 0.05) and those who worked in faith-based health facilities (AME = 18, SE = 0.07, p < 0.05) were more likely to participate in a COVID-19 vaccine trial. Female HCWs (AME = − 11, SE = 0.04, p < 0.05) and those with lower educational qualification were less likely to accept a COVID-19 vaccine (AME = − 0.16, SE = 0.08, p < 0.1). Reasons cited for unwillingness to participate in a COVID-19 vaccine trial or uptake the vaccine were mainly fear, safety concerns, mistrust, uncertainty, spiritual and religious beliefs.ConclusionsAcceptance of the COVID-19 vaccine appear to be high among HCWs; conversely, willingness to volunteer for the vaccine trial was low. Continuous targeted and integrated public health education for HCWs will enhance vaccine acceptability to promote safety and population health in the global south as Ghana intensifies efforts to produce COVID-19 vaccines locally.

Trial participants' rights after authorisation of COVID-19 vaccines

EPH103 COVID-19 Vaccination Among Pregnant Women in the US: A Systematic Review

Current COVID-19 vaccine trials in high-income countries: are placebo-controlled trials ethical?

A World Health Organization (WHO) Ad Hoc Expert Group on the Next Steps for Covid-19 Vaccine Evaluation recently recommended placebo-controlled trials (PCT) of Covid-19 vaccines. PCTs are ethically acceptable when there is no proven effective and safe treatment for a certain condition. However, there are already some vaccines that have been approved and which have high levels of efficacy and safety. Any new vaccine under development must be tested against the most effective vaccines available. PCTs go against the participants' best interests, by putting them in a position of disadvantage while taking part in a trial, compared with people who are not in the trial and who could get vaccinated. Particularly in high-income countries, many people are getting vaccinated. This means that, following a recent trend in clinical trials, PCTs would have to be conducted in low- and middle-income countries, where there a number of advantages for drug companies, but where fatality rates of Covid-19 are, in many cases, much higher. For this and other reasons having to do with equal rights, participants in control groups should be protected with the most effective vaccines available.

IntroductionWe analyzed the exclusion of pregnant and breastfeeding individuals and those capable of pregnancy in coronavirus disease 2019 (COVID-19) vaccine and clinical treatment trials.MethodsInclusion and exclusion criteria were extracted from all listed COVID-19 vaccine and treatment clinical trials from May 1, 2020, to October 31, 2020, using the U.S. National Library of Medicine database. We report rates of rates of exclusion for pregnant and lactating individuals and requirements for contraception for pregnancy-capable participants in COVID-19 vaccine and treatment clinical trials. The analysis included the association between clinical trial exclusion and vaccine and treatment type, study location, sponsor, and phase.ResultsPregnant and lactating individuals were explicitly excluded from most COVID-19 vaccine and treatment clinical trials. Of the 90 vaccine trials, 88 (97.8%) excluded pregnant individuals, 73 (81.1%) excluded lactating individuals, and 56 (62.2%) required contraception use. Of the 495 treatment trials, 350 (70.7%) excluded pregnant individuals, 269 (54.3%) excluded lactating individuals, and 91 (18.4%) required contraception use. Although vaccine type was not associated with pregnancy exclusion, it was associated with lactation exclusion (p = .01) and contraception requirement (p < .001). Treatment type was associated with pregnancy exclusion, lactation exclusion, and contraception requirement (all p < .001).ConclusionsCOVID-19 vaccination and treatment clinical trials mirrored historical trends restricting participation owing to pregnancy, lactation, and contraception nonuse, despite known safety profiles. People of childbearing potential should be considered for and afforded the same opportunity as males to make informed decisions on study participation, particularly in the setting of a global pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented global toll and vaccination is needed to restore healthy living. Timely inclusion of children in vaccination trials is critical. We surveyed caregivers of children seeking care in 17 Emergency Departments (ED) across 6 countries during the peak of the pandemic to identify factors associated with intent to participate in COVID-19 vaccine trials. Questions about child and parent characteristics, COVID-19 expressed concerns and parental attitudes toward participation in a trial were asked. Of 2768 completed surveys, 18.4% parents stated they would enroll their child in a clinical trial for a COVID-19 vaccine and 14.4% would agree to a randomized placebo-controlled study. Factors associated with willingness to participate were parents agreeing to enroll in a COVID-19 vaccine trial themselves (Odds Ratio (OR) 32.9, 95% Confidence Interval (CI) (21.9–51.2)) having an older child (OR 1.0 (1.0–1.01)), having children who received all vaccinations based on their country schedule (OR 2.67 (1.35–5.71)) and parents with high school education or lower (OR 1.79 (1.18–2.74)). Mothers were less likely to enroll their child in a trial (OR 0.68 (0.47–0.97)). Only one fifth of families surveyed will consider enrolling their child in a vaccine trial. Parental interest in participation, history of vaccinating their child, and the child being older all are associated with parents allowing their child to participate in a COVID vaccine trial. This information may help decision-makers and researchers shape their strategies for trial design and participation engagement in upcoming COVID19 vaccination trials.

BackgroundCoronavirus disease 2019 (COVID-19) has already claimed over four million lives globally and over 800 deaths in Ghana. The COVID-19 vaccine is a key intervention towards containing the pandemic. Over three billion doses of the vaccine have already been administered globally and over 800,000 doses administered in Ghana, representing less than 5% vaccination coverage. Fear, uncertainty, conspiracy theories and safety concerns remain important threats to, a successful rollout of the vaccine if not managed well.ObjectiveAscertain the predictors of citizens’ probability of participating in a COVID-19 vaccine trial and subsequently accept the vaccine when given the opportunity.MethodologyThe study was an online nation-wide survey among community members (n = 1556) from 18th September to 23rd October, 2020 in the 16 regions in Ghana. Binary probit regression analysis with marginal effect estimations was employed to ascertain the predictors of community members’ willingness to participate in a COVID-19 vaccine trial and uptake the vaccine.ResultsApproximately 60% of respondents said they will not participate in a COVID-19 vaccine trial; 65% will take the vaccine, while 69% will recommend it to others. Willingness to voluntarily participate in COVID-19 vaccine trial, uptake the vaccine and advise others to do same was higher among adults aged 18–48 years, the unmarried and males (p < 0.05). Significant predictors of unwillingness to participate in the COVID-19 vaccine trial and uptake of the vaccine are: married persons, females, Muslims, older persons, residents of less urbanised regions and persons with lower or no formal education (p < 0.05). Predominant reasons cited for unwillingness to participate in a COVID-19 vaccine trial and take the vaccine included fear, safety concerns, lack of trust in state institutions, uncertainty, political connotations, spiritual and religious beliefs.ConclusionThe probability of accepting COVID-19 vaccine among the adult population in Ghana is high but the country should not get complacent because fear, safety and mistrust are important concerns that have the potential to entrench vaccine hesitancy. COVID-19 vaccine rollout campaigns should be targeted and cognisant of the key predictors of citizens’ perceptions of the vaccine. These lessons when considered will promote Ghana’s efforts towards vaccinating at least 20 million people to attain herd immunity.

The Egyptian clinical trials’ registry profile: Analysis of three trial registries (International Clinical Trials Registry Platform, Pan-African Clinical Trials Registry and clinicaltrials.gov)

BackgroundThe COVID-19 pandemic marked a unique period characterised by an extraordinary global virus spread. The collective effort to halt the transmission of the virus led to various public health initiatives, including a variety of COVID-19 vaccine trials. Many of these trials used adaptive methods to address the pandemic’s challenges, such as the need for rapid recruitment. These adaptive methods allow for modifications to the trial procedures without undermining the trial’s integrity, making the research process more flexible and efficient. However, recruiting participants for vaccine trials remains a considerable challenge. The aim of this qualitative evidence synthesis (QES) is to explore the factors that influence a person’s decision to participate in a COVID-19 vaccine trial. Lessons learned from this could help shape future trials’ design and conduct, particularly those conducted within a pandemic.MethodsWe conducted a systematic search for qualitative studies and mixed methods studies with a qualitative component in the WHO COVID-19 Research Database, MEDLINE, CINAHL, PsycINFO, Epistemomikos, Online Resource for Research in Clinical Trials (ORCCA), and the Cochrane COVID-19 Study Register. We used the best-fit framework synthesis approach and the Social Ecological Model as an a priori framework. We used the GRADE-CERQual approach to assess our confidence in the review findings.ResultsFive studies involving 539 participants were included. One of these studies included participants in a COVID-19 vaccine trial. In three of the studies, participants were asked hypothetically about their attitudes. Another study included people who had either not responded to or declined an invitation to participate in a COVID-19 vaccine trial.We developed six themes outlining the factors that influence a person’s decision to participate in a COVID-19 vaccine trial: (1) personal gains, (2) perceived risk, (3) influence of family and community, (4) contributing for others, (5) institutional trust and mistrust, and (6) accessibility of the trial.ConclusionThis review sheds light on how people perceive the potential personal, family, and community advantages of trial participation and how these perceptions may be weighed against concerns about vaccine safety. The findings also point toward specific aspects of trial methodology to consider when designing COVID-19 vaccine trials.Graphical