Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey), completed an online survey. From 15 eligible groups, those that were more frequently declared underserved/hard-to-reach in vaccine research were ethnic minorities (76.5%), persons experiencing homelessness (70.6%), illegal workers and refugees (64.7%, each). When prioritization for education on vaccine trials was considered, ethnic groups, migrants, and immigrants (5/17, 29.4%) were the groups most frequently identified by the NC as top targets. The most prominent barriers in vaccine trial participation affecting all groups were low levels of health literacy, reluctance to participate in trials due to engagement level, and low levels of trust in vaccines/vaccinations. This study highlighted population groups considered underserved/hard-to-reach in countries contained within the European region, and the respective barriers these groups face when participating in clinical studies. Our findings aid with the design of tailored interventions (within-and across-countries of the European region) and with the development of strategies to overcome major barriers in phase 2 and phase 3 vaccine trial participation.

2nd Department of Pediatrics School of Medicine National and Kapodistrian University of Athens 11527 Athens Greece

Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf Department 1 of Internal Medicine Faculty of Medicine and University Hospital Cologne University of Cologne 50931 Cologne Germany

Center for Molecular Medicine Cologne Faculty of Medicine and University Hospital Cologne University of Cologne 50931 Cologne Germany

Centre for Experimental Pathogen Host Research School of Medicine University College Dublin D04 V1W8 Dublin Ireland

Centro Hospitalar Universitário do Porto 4099 001 Porto Portugal

Centro Nacional de Microbiología Instituto de Salud Carlos 3 28220 Madrid Spain

Clinical Trials Centre Cologne Faculty of Medicine and University Hospital Cologne University of Cologne 50935 Cologne Germany

Collaborative Center for Clinical Epidemiology and Outcomes Research 15451 Athens Greece

Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases Institute of Translational Research Faculty of Medicine and University Hospital Cologne University of Cologne 50931 Cologne Germany

Czech Clinical Research Infrastructure Network 62500 Brno Czech Republic

Department of Clinical Pharmacology Medical University Vienna 1090 Vienna Austria

Department of Infectious Diseases and Clinical Microbiology Faculty of Medicine Haceteppe University Ankara 06230 Turkey

Department of Infectious Diseases Karolinska University Hospital 17177 Stockholm Sweden

Department of Medicine Division of Infectious Diseases Karolinska Institutet 17177 Stockholm Sweden

Department of Pharmacology Faculty of Medicine Masaryk University 60177 Brno Czech Republic

European Vaccine Initiative 69115 Heidelberg Germany

German Centre for Infection Research Partner Site Bonn Cologne 38124 Cologne Germany

Hospital La Paz Institute for Health Research 28046 Madrid Spain

Infectious Diseases Department of Diagnostic and Public Health University of Verona 37134 Verona Italy

Influenza Centre Department of Clinical Science University of Bergen 5020 Bergen Norway

Institute of Clinical Medicine Medical Faculty Vilnius University 03101 Vilnius Lithuania

Ministry of Health of Israel Jerusalem 1176 Israel

National Koranyi Institute for Pulmonology 1121 Budapest Hungary

School of Medicine European University Cyprus Nicosia 2404 Cyprus

Servicio Madrileño de Salud 28046 Madrid Spain

University Hospital Brno 62500 Brno Czech Republic

VAXINFECTIO Centre of Evaluation of Vaccination Faculty of Medicine and Health Science Universiteit Antwerpen 2610 Antwerp Belgium

Vilnius University Hospital Santaros Klinikos Medical Faculty Vilnius University 03101 Vilnius Lithuania

See more in PubMed

Park J.J.H., Mogg R., Smith G.E., Nakimuli-Mpungu E., Jehan F., Rayner C.R., Condo J., Decloedt E.H., Nachega J.B., Reis G., et al. How COVID-19 has fundamentally changed clinical research in global health. Lancet Glob. Health. 2021;9:e711–e720. doi: 10.1016/S2214-109X(20)30542-8. PubMed DOI PMC

Xiao H., Vaidya R., Liu F., Chang X., Xia X., Unger J.M. Sex, Racial, and Ethnic Representation in COVID-19 Clinical Trials: A Systematic Review and Meta-analysis. JAMA Intern. Med. 2023;183:50–60. doi: 10.1001/jamainternmed.2022.5600. PubMed DOI PMC

Flanagan S.M., Hancock B. ‘Reaching the hard to reach’—Lessons learned from the VCS (voluntary and community Sector). A qualitative study. BMC Health Serv. Res. 2010;10:92. doi: 10.1186/1472-6963-10-92. PubMed DOI PMC

Avnir Y., Watson C.T., Glanville J., Peterson E.C., Tallarico A.S., Bennett A.S., Qin K., Fu Y., Huang C.-Y., Beigel J.H., et al. IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity. Sci. Rep. 2016;6:20842. doi: 10.1038/srep20842. PubMed DOI PMC

Wang L.-Y., Hu C.-T., Ho T.-Y., Lin H.H. Geographic and ethnic variations of long-term efficacy and immunogenicity of hepatitis B vaccination in Hualien, a HBV hyperendemic area. Vaccine. 2006;24:4427–4432. doi: 10.1016/j.vaccine.2005.12.069. PubMed DOI

Liu G., Carter B., Gifford D.K. Predicted Cellular Immunity Population Coverage Gaps for SARS-CoV-2 Subunit Vaccines and Their Augmentation by Compact Peptide Sets. Cell Syst. 2021;12:102–107.e104. doi: 10.1016/j.cels.2020.11.010. PubMed DOI PMC

Gray D.M., II, Nolan T.S., Gregory J., Joseph J.J. Diversity in clinical trials: An opportunity and imperative for community engagement. Lancet Gastroenterol. Hepatol. 2021;6:605–607. doi: 10.1016/S2468-1253(21)00228-4. PubMed DOI

VACCELERATE-European Corona Vaccine Trial Accelerator Platform. [(accessed on 12 April 2023)]. Available online: https://vaccelerate.eu/

Salmanton-García J., Stewart F.A., Heringer S., Koniordou M., Álvarez-Barco E., Argyropoulos C.D., Themistocleous S.C., Valle-Simón P., Spivak O., Součková L., et al. VACCELERATE Volunteer Registry: A European study participant database to facilitate clinical trial enrolment. Vaccine. 2022;40:4090–4097. doi: 10.1016/j.vaccine.2022.05.022. PubMed DOI PMC

Salmanton-García J., Wipfler P., Valle-Simón P., Merakou C., Kopsidas I., Bethe U., Steinbach A., Spivak O., Součková L., Mendonça M.A., et al. VACCELERATE Site Network: Real-time definition of clinical study capacity in Europe. Vaccine. 2023;41:3915–3922. doi: 10.1016/j.vaccine.2023.05.006. PubMed DOI PMC

Ekezie W., Awwad S., Krauchenberg A., Karara N., Dembiński Ł., Grossman Z., Del Torso S., Dornbusch H.J., Neves A., Copley S., et al. Access to Vaccination among Disadvantaged, Isolated and Difficult-to-Reach Communities in the WHO European Region: A Systematic Review. Vaccines. 2022;10:1038. doi: 10.3390/vaccines10071038. PubMed DOI PMC

Robinson R., Nguyen E., Wright M., Holmes J., Oliphant C., Cleveland K., Nies M.A. Factors contributing to vaccine hesitancy and reduced vaccine confidence in rural underserved populations. Humanit. Soc. Sci. Commun. 2022;9:416. doi: 10.1057/s41599-022-01439-3. PubMed DOI PMC

Argyropoulos C.D., Leckler J., Salmanton-García J., Constantinou M., Alexandrou A., Themistocleous S., Noula E., Shiamakkides G., Nearchou A., Stewart F.A., et al. Enhancing Public Health Communication Regarding Vaccine Trials: Design and Development of the Pan-European VACCELERATE Toolkit. JMIR Public Health Surveill. 2023;9:e44491. doi: 10.2196/44491. PubMed DOI PMC

Shaghaghi A., Bhopal R.S., Sheikh A. Approaches to Recruiting ‘Hard-To-Reach’ Populations into Re-search: A Review of the Literature. Health Promot. Perspect. 2011;1:86–94. doi: 10.5681/hpp.2011.009. PubMed DOI PMC

Ojha R.P., Jackson B.E., Lu Y., Burton M., Blair S.E., MacDonald B.R., Chu T.C., Teigen K.J., Acosta M. Participation and retention can be high in randomized controlled trials targeting underserved populations: A systematic review and meta-analysis. J. Clin. Epidemiol. 2018;98:154–157. doi: 10.1016/j.jclinepi.2017.11.014. PubMed DOI

Treweek S., Banister K., Bower P., Cotton S., Devane D., Gardner H.R., Isaacs T., Nestor G., Oshisanya A., Parker A., et al. Developing the INCLUDE Ethnicity Framework—A tool to help trialists design trials that better reflect the communities they serve. Trials. 2021;22:337. doi: 10.1186/s13063-021-05276-8. PubMed DOI PMC

Witham M.D., Anderson E., Carroll C., Dark P.M., Down K., Hall A.S., Knee J., Maier R.H., Mountain G.A., Nestor G., et al. Developing a roadmap to improve trial delivery for under-served groups: Results from a UK multi-stakeholder process. Trials. 2020;21:694. doi: 10.1186/s13063-020-04613-7. PubMed DOI PMC

Kelsey M.D., Patrick-Lake B., Abdulai R., Broedl U.C., Brown A., Cohn E., Curtis L.H., Komelasky C., Mbagwu M., Mensah G.A., et al. Inclusion and diversity in clinical trials: Actionable steps to drive lasting change. Contemp. Clin. Trials. 2022;116:106740. doi: 10.1016/j.cct.2022.106740. PubMed DOI PMC

Etti M., Fofie H., Razai M., Crawshaw A.F., Hargreaves S., Goldsmith L.P. Ethnic minority and migrant underrepresentation in COVID-19 research: Causes and solutions. eClinicalMedicine. 2021;36:100903. doi: 10.1016/j.eclinm.2021.100903. PubMed DOI PMC

Amorrortu R.P., Arevalo M., Vernon S.W., Mainous A.G., Diaz V., McKee M.D., Ford M.E., Tilley B.C. Recruitment of racial and ethnic minorities to clinical trials conducted within specialty clinics: An intervention mapping approach. Trials. 2018;19:115. doi: 10.1186/s13063-018-2507-9. PubMed DOI PMC

Taylor O., Loubiere S., Tinland A., Vargas-Moniz M., Spinnewijn F., Manning R., Gaboardi M., Wolf J.R.L.M., Bokszczanin A., Bernad R., et al. Lifetime, 5-year and past-year prevalence of homelessness in Europe: A cross-national survey in eight European nations. BMJ Open. 2019;9:e033237. doi: 10.1136/bmjopen-2019-033237. PubMed DOI PMC

Ojo-Fati O., Joseph A.M., Ig-Izevbekhai J., Thomas J.L., Everson-Rose S.A., Pratt R., Raymond N., Cooney N.L., Luo X., Okuyemi K.S. Practical issues regarding implementing a randomized clinical trial in a homeless population: Strategies and lessons learned. Trials. 2017;18:305. doi: 10.1186/s13063-017-2046-9. PubMed DOI PMC

Young M.-E.D.T., Madrigal D.S. Documenting legal status: A systematic review of measurement of undocumented status in health research. Public Health Rev. 2017;38:26. doi: 10.1186/s40985-017-0073-4. PubMed DOI PMC

Magee L., Knights F., McKechnie D.G.J., Al-bedaery R., Razai M.S. Facilitators and barriers to COVID-19 vaccination uptake among ethnic minorities: A qualitative study in primary care. PLoS ONE. 2022;17:e0270504. doi: 10.1371/journal.pone.0270504. PubMed DOI PMC

Luís C., Di Marzo V.R., Kaur M., Argyropoulos C.D., Devane D., Stewart F.A., Antoniou G., Hendrickx G., Askling H.H., Hellemans M. Vaccination rates in Europe are not associated with online media intensity. J. Sci. Commun. 2022;21 doi: 10.22323/2.21050205. DOI

Daniels D., Imdad A., Buscemi-Kimmins T., Vitale D., Rani U., Darabaner E., Shaw A., Shaw J. Vaccine hesitancy in the refugee, immigrant, and migrant population in the United States: A systematic review and meta-analysis. Hum. Vaccines Immunother. 2022;18:2131168. doi: 10.1080/21645515.2022.2131168. PubMed DOI PMC

Hildreth J.E.K., Alcendor D.J. Targeting COVID-19 Vaccine Hesitancy in Minority Populations in the US: Implications for Herd Immunity. Vaccines. 2021;9:489. doi: 10.3390/vaccines9050489. PubMed DOI PMC

Heller C., Balls-Berry J.E., Nery J.D., Erwin P.J., Littleton D., Kim M., Kuo W.P. Strategies addressing barriers to clinical trial enrollment of underrepresented populations: A systematic review. Contemp. Clin. Trials. 2014;39:169–182. doi: 10.1016/j.cct.2014.08.004. PubMed DOI PMC

Yasmin F., Najeeb H., Moeed A., Naeem U., Asghar M.S., Chughtai N.U., Yousaf Z., Seboka B.T., Ullah I., Lin C.Y., et al. COVID-19 Vaccine Hesitancy in the United States: A Systematic Review. Front. Public Health. 2021;9:770985. doi: 10.3389/fpubh.2021.770985. PubMed DOI PMC

Tankwanchi A.S., Bowman B., Garrison M., Larson H., Wiysonge C.S. Vaccine hesitancy in migrant communities: A rapid review of latest evidence. Curr. Opin. Immunol. 2021;71:62–68. doi: 10.1016/j.coi.2021.05.009. PubMed DOI

Gupta P.S., Mohareb A.M., Valdes C., Price C., Jollife M., Regis C., Munshi N., Taborda E., Lautenschlager M., Fox A., et al. Expanding COVID-19 vaccine access to underserved populations through implementation of mobile vaccination units. Prev. Med. 2022;163:107226. doi: 10.1016/j.ypmed.2022.107226. PubMed DOI PMC

Allison K., Patel D., Kaur R. Assessing Multiple Factors Affecting Minority Participation in Clinical Trials: Development of the Clinical Trials Participation Barriers Survey. Cureus. 2022;14:e24424. doi: 10.7759/cureus.24424. PubMed DOI PMC

Staples J.N., Lester J., Li A., Walsh C., Cass I., Karlan B.Y., Bresee C., Rimel B.J. Language as a barrier to cancer clinical trial accrual: Assessing consenting team knowledge and practices for cancer clinical trial consent among low English fluency patients. Appl. Cancer Res. 2018;38:14. doi: 10.1186/s41241-018-0065-9. DOI

Woll A., Quick K.K., Mazzei C., Selameab T., Miller J.L. Working with Interpreters as a Team in Health Care (with Care) Curriculum Tool Kit for Oral Health Professions. MedEdPORTAL. 2020;16:10894. doi: 10.15766/mep_2374-8265.10894. PubMed DOI PMC

U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) Enhancing the Diversity of Clinical Trial Populations—Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry. Food and Drug Administration; Silver Spring, MD, USA: 2020.