How inclusive were UK-based randomised controlled trials of COVID-19 vaccines? A systematic review investigating enrolment of Black adults and adult ethnic minorities.

OBJECTIVES: To establish if Black adults and adult ethnic minorities, defined as any group except White British, were represented in UK-based COVID-19 vaccination randomised controlled trials (RCTs) when compared to corresponding UK population proportions, based on 2011 census data. DESIGN: Systematic review of COVID-19 Randomised Controlled Vaccine Trials SETTING: United Kingdom PARTICIPANTS: Randomised Controlled Trials of COVID-19 vaccines conducted in the UK were systematically reviewed following PRISMA guidelines. MeSH terms included "Covid-19 vaccine", "Ad26COVS1", and "BNT162 Vaccine" with keywords such as [covishield OR coronavac OR Vaxzevria OR NVX-CoV2373] also used. Studies that provided (A) participant demographics and (B) full eligibility criteria were included. The following key data was extracted for analysis: number of participants analysed, number of Black adults and number of adult minority ethnicity participants. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is the mean percentage of Black adults randomised to COVID-19 vaccine trials deemed eligible within this review. The secondary outcome is the mean percentage of adult ethnic minorities randomised. RESULTS: The final review included 7 papers and a total of 87 sets of data collated from trial sites across the UK. The standard mean percentage of Black adults included in the trials (0.59%, 95% CI: 0.13% - 1.05%) was significantly lower compared to the recorded Black adult population (2.67%) indicating that they were under-served in UK based COVID-19 vaccine RCTs (p < 0.001). Adult ethnic minority presence (8.94%, 95% CI: 2.07% - 15.80%) was also lower than census data (16.30%), indicating they were also under-served (p = 0.039). CONCLUSION: The findings show that COVID-19 vaccine trials failed to adequately randomise proportionate numbers of Black adults and adult minority ethnicities. More inclusive practices must be developed and implemented in the recruitment of underserved groups to understand the true impact of COVID-19.

Shining a spotlight on the inclusion of disabled participants in clinical trials: a mixed methods study.

BACKGROUND: It is crucial to include a wide range of the population in clinical trials for the outcome to be applicable in real-world settings. Existing literature indicates that under-served groups, including disabled people, have been excluded from participating in clinical trials without justification. Exclusion from clinical trials exacerbates disparities in healthcare and diminishes the benefits for excluded populations. Therefore, this study was conducted to investigate potential obstacles that prevent disabled people from participating in clinical trials in the United Kingdom (UK). METHODS: The study was carried out through an explanatory sequential mixed methods design. The Imperial Clinical Trials Unit devised and implemented an online questionnaire-based survey (with open/closed-ended questions) and an online focus group discussion. The target population were disabled people, family members/carers of disabled people and staff involved in clinical trials, whereupon the sample was recruited by convenience sampling methods via posters and emails through various networks. The Qualtrics XM survey system was used as the host platform for the online survey, and Microsoft Teams was used for an online focus group discussion. The focus group discussion was conducted to gain a deeper understanding of the themes identified from the survey responses. We analysed responses to the survey via descriptive analysis and used thematic analysis to synthesise the free-text answers from the survey and focus group discussion. RESULTS: We received 45 responses to the survey questionnaire and 5 disabled people took part in a focus group discussion. Our findings highlighted the differences between the perspectives of researchers and those "being researched" and different types of barriers experienced by disabled people: opportunity barriers (inadequate recruitment strategy and ambiguous eligibility criteria), awareness barriers (perception of disability) and acceptance/refusal barriers (available support and adjustment, and sharing of trial results). CONCLUSION: Our findings support perspectives drawn from the Ford Framework regarding the need to consider all barriers, not just up to the point of enrolment into trials but also beyond the point of inclusion in clinical trials. We support calls for the introduction of legislation on including disabled people in clinical trials, implementation of industry/community-wide participatory approaches and the development of guidelines, a combined public-private approach.

Treating severe paediatric asthma with mepolizumab or omalizumab: a protocol for the TREAT randomised non-inferiority trial.

INTRODUCTION: A minority of school-aged children with asthma have persistent poor control and experience frequent asthma attacks despite maximal prescribed maintenance therapy. These children have higher morbidity and risk of death. The first add-on biologic therapy, omalizumab, a monoclonal antibody that blocks immunoglobulin (Ig)E, was licensed for children with severe asthma in 2005. While omalizumab is an effective treatment, non-response is common. A second biologic, mepolizumab which blocks interleukin 5 and targets eosinophilic inflammation, was licensed in 2018, but the licence was granted by extrapolation of adult clinical trial data to children. This non-inferiority (NI) trial will determine whether mepolizumab is as efficacious as omalizumab in reducing asthma attacks in children with severe therapy resistant asthma (STRA) and refractory difficult asthma (DA). METHODS AND ANALYSIS: This is an ongoing multicentre 1:1 randomised NI open-label trial of mepolizumab and omalizumab. Up to 150 children and young people (CYP) aged 6-17 years with severe asthma will be recruited from specialist paediatric severe asthma centres in the UK. Prior to randomisation, children will be monitored for medication adherence for up to 16 weeks to determine STRA and refractory DA diagnoses. Current prescribing recommendations of serum IgE and blood eosinophils will not influence eligibility or enrolment. The primary outcome is the 52-week asthma attack rate. Bayesian analysis using clinician-elicited prior distributions will be used to calculate the posterior probability that mepolizumab is not inferior to omalizumab. Secondary outcomes include Composite Asthma Severity Index, Paediatric Asthma Quality of Life Questionnaire, lung function measures (forced expiratory volume in one second (FEV1), bronchodilator reversibility), fractional exhaled nitric oxide, Asthma Control Test (ACT), health outcomes EuroQol 5 Dimension (EQ-5D) and optimal serum IgE and blood eosinophil levels that may predict a response to therapy. These outcomes will be analysed in a frequentist framework using longitudinal models. ETHICS AND DISSEMINATION: The study has been approved by the South Central-Berkshire Research Ethics Committee REC Number 19/SC/0634 and had Clinical Trials Authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT 2019-004085-17). All parents/legal guardians will give informed consent for their child to participate in the trial, and CYP will give assent to participate. The results will be published in peer-reviewed journals, presented at international conferences and disseminated via our patient and public involvement partners. TRIAL REGISTRATION NUMBER: ISRCTN12109108; EudraCT Number: 2019-004085-17.