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Review

Vaccine clinical trials in low- and middle-income countries: a brief review of standard, newer and proposed approaches

ORCID Icon &
Pages 1595-1602 | Received 13 Jun 2022, Accepted 15 Sep 2022, Published online: 21 Sep 2022

References

  • Rts SCTP. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet. 2015;386(9988):31–45.
  • Pan WK, Seidman JC, Ali A, et al. Oral polio vaccine response in the MAL-ED birth cohort study: considerations for polio eradication strategies. Vaccine. 2019;37(2):352–365.
  • Gladstone BP, Ramani S, Mukhopadhya I, et al. Protective effect of natural rotavirus infection in an Indian birth cohort. N Engl J Med. 2011;365(4):337–346.
  • Lopman BA, Pitzer VE, Sarkar R, et al. Understanding reduced rotavirus vaccine efficacy in low socio-economic settings. PLoS One. 2012;7(8):e41720.
  • Isanaka S, Guindo O, Langendorf C, et al., Efficacy of a low-cost, heat-stable oral rotavirus vaccine in Niger. N Engl J Med. 2017;376(12):1121–1130.
  • Bravo L, Smolenov I, Han HH, et al. Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2022;399(10323):461–472.
  • Hayman B, Bowles A, Evans B, et al. Advancing innovation for vaccine manufacturers from developing countries: prioritization, barriers, opportunities. Vaccine. 2021;39(8):1190–1194.
  • WHO. Prequalification of medical products (IVDs, medicines, vaccines and immunization devices, vector control). https://extranet.who.int/pqweb/ Cited 2022 Mar 11
  • Deen JL, Clemens JD. Issues in the design and implementation of vaccine trials in less developed countries. Nat Rev Drug Discov. 2006;5(11):932–940.
  • Kuhlmann J. Drug research: from the idea to the product. Int J Clin Pharmacol Ther. 1997;35(12):541–552.
  • Park JJH, Grais RF, Taljaard M, et al., Urgently seeking efficiency and sustainability of clinical trials in global health. Lancet Glob Health. 2021;9(5):e681–e690.
  • Holmgren J. Modern history of cholera vaccines and the pivotal role of icddr,b. J Infect Dis. 2021;224(12 Suppl 2):S742–S748.
  • Jertborn M, Svennerholm AM, Holmgren J. Safety and immunogenicity of an oral recombinant cholera B subunit-whole cell vaccine in Swedish volunteers. Vaccine. 1992;10(2):130–132.
  • Jertborn M, Svennerholm AM, Holmgren J. Evaluation of different immunization schedules for oral cholera B subunit-whole cell vaccine in Swedish volunteers. Vaccine. 1993;11(10):1007–1012.
  • Clemens JD, Stanton BF, Chakraborty J, et al. B subunit-whole cell and whole cell-only oral vaccines against cholera: studies on reactogenicity and immunogenicity. J Infect Dis. 1987;155(1):79–85.
  • Clemens JD, Sack DA, Harris JR, et al. Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up. Lancet. 1990;335(8684):270–273.
  • Anh DD, Canh DG, Lopez AL, et al. Safety and immunogenicity of a reformulated Vietnamese bivalent killed, whole-cell, oral cholera vaccine in adults. Vaccine. 2007;25(6):1149–1155.
  • Mahalanabis D, Lopez AL, Sur D, et al. A randomized, placebo-controlled trial of the bivalent killed, whole-cell, oral cholera vaccine in adults and children in a cholera endemic area in Kolkata, India. PLoS One. 2008;3(6):e2323.
  • Sur D, Lopez AL, Kanungo S, et al. Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trial. Lancet. 2009;374(9702):1694–1702.
  • Sur D, Kanungo S, Sah B, et al. Efficacy of a low-cost, inactivated whole-cell oral cholera vaccine: results from 3 years of follow-up of a randomized, controlled trial. PLoS Negl Trop Dis. 2011;5(10):e1289.
  • Bhattacharya SK, Sur D, Ali M, et al. 5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2013;13(12):1050–1056.
  • WHO. Meeting of the strategic advisory group of experts on immunization, October 2009 – conclusions and recommendations. Weekly Epidemiological Rec. 2009;50(84):526–528.
  • Desai SN, Pezzoli L, Alberti KP, et al. Achievements and challenges for the use of killed oral cholera vaccines in the global stockpile era. Hum Vaccin Immunother. 2017;13(3):579–587.
  • Pezzoli L, Oral Cholera Vaccine Working Group of the Global Task Force on Cholera C. Global oral cholera vaccine use, 2013-2018. Vaccine. 2020;38(Suppl 1):A132–A140.
  • World Health Organization. (2013). Correlates of vaccine-induced protection: methods and implications. World Health Organization. https://apps.who.int/iris/handle/10665/84288 Cited 2022 Mar 7
  • Fritzell B. Bridging studies *. Dev Biol Stand. 1998;95:181–188.
  • Schumi J, Wittes JT. Through the looking glass: understanding non-inferiority. Trials. 2011;12(106). DOI:10.1186/1745-6215-12-106
  • Baik YO, Choi SK, Kim JW, et al. Safety and immunogenicity assessment of an oral cholera vaccine through phase I clinical trial in Korea. J Korean Med Sci. 2014;29(4):494–501.
  • Baik YO, Choi SK, Olveda RM, et al. A randomized, non-inferiority trial comparing two bivalent killed, whole cell, oral cholera vaccines (Euvichol vs Shanchol) in the Philippines. Vaccine. 2015;33(46):6360–6365.
  • Metzger WG, Ehni HJ, Kremsner PG, et al. Experimental infections in humans-historical and ethical reflections. Trop Med Int Health. 2019;24(12):1384–1390.
  • Msusa KP, Rogalski-Salter T, Mandi H, et al. Critical success factors for conducting human challenge trials for vaccine development in low- and middle-income countries. Vaccine. 2022;40(9):1261–1270.
  • Black RE, Levine MM, Clements ML, et al. Protective efficacy in humans of killed whole-vibrio oral cholera vaccine with and without the B subunit of cholera toxin. Infect Immun. 1987;55(5):1116–1120.
  • Burki T. Typhoid conjugate vaccine gets WHO prequalification. Lancet Infect Dis. 2018;18(3):258.
  • Mohan VK, Varanasi V, Singh A, et al. Safety and immunogenicity of a Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar-TCV) in healthy infants, children, and adults in typhoid endemic areas: a multicenter, 2-cohort, open-label, double-blind, randomized controlled phase 3 study. Clin Infect Dis. 2015;61(3):393–402.
  • Jin C, Gibani MM, Moore M, et al. Efficacy and immunogenicity of a Vi-tetanus toxoid conjugate vaccine in the prevention of typhoid fever using a controlled human infection model of Salmonella Typhi: a randomised controlled, phase 2b trial. Lancet. 2017;390(10111):2472–2480.
  • Shakya M, Colin-Jones R, Theiss-Nyland K, et al. Phase 3 efficacy analysis of a typhoid conjugate vaccine trial in Nepal. N Engl J Med. 2019;381(23):2209–2218.
  • Qadri F, Khanam F, Liu X, et al. Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial. Lancet. 2021;398(10301):675–684.
  • Patel PD, Patel P, Liang Y, et al. Safety and efficacy of a typhoid conjugate vaccine in Malawian Children. N Engl J Med. 2021;385(12):1104–1115.
  • Health Organization W, World Health O. Typhoid vaccines: WHO position paper, March 2018 - recommendations. Vaccine. 2019;37(2):214–216.
  • Bhatt DL, Mehta C, Drazen JM. Adaptive designs for clinical trials. N Engl J Med. 2016;375(1):65–74.
  • Thorlund K, Haggstrom J, Park JJ, et al. Key design considerations for adaptive clinical trials: a primer for clinicians. BMJ. 2018;360:k698.
  • WHO. Design of vaccine efficacy trials to be used during public health emergencies – points of considerations and key principles. https://www.who.int/docs/default-source/blue-print/working-group-for-vaccine-evaluation-(4th-consultation)/ap1-guidelines-online-consultation.pdf Cited 2022 Mar 11).
  • Lang T. Adaptive trial design: could we use this approach to improve clinical trials in the field of global health? Am J Trop Med Hyg. 2011;85(6):967–970.
  • Donner A, Klar N. Methods for comparing event rates in intervention studies when the unit of allocation is a cluster. Am J Epidemiol. 1994;140(3):279–289. discussion 300-271.
  • Hayes RJ, Alexander ND, Bennett S, et al. Design and analysis issues in cluster-randomized trials of interventions against infectious diseases. Stat Methods Med Res. 2000;9(2):95–116.
  • Dron L, Taljaard M, Cheung YB, et al., The role and challenges of cluster randomised trials for global health. Lancet Glob Health. 2021;9(5):e701–e710.
  • Hitchings MDT, Lipsitch M, Wang R, et al. Competing effects of indirect protection and clustering on the power of cluster-randomized controlled vaccine trials. Am J Epidemiol. 2018;187(8):1763–1771.
  • Sur D, Deen JL, Manna B, et al. The burden of cholera in the slums of Kolkata, India: data from a prospective, community based study. Arch Dis Child. 2005;90(11):1175–1181.
  • Sur D, Manna B, Deb AK, et al. Factors associated with reported diarrhoea episodes and treatment-seeking in an urban slum of Kolkata, India. J Health Popul Nutr. 2004;22(2):130–138.
  • Poulos C, Riewpaiboon A, Stewart JF, et al. Costs of illness due to endemic cholera. Epidemiol Infect. 2012;140(3):500–509.
  • Jeuland M, Cook J, Poulos C, et al., Group DCES. Cost-effectiveness of new-generation oral cholera vaccines: a multisite analysis. Value Health. 2009;12(6):899–908.
  • Ali M, Sur D, You YA, et al. Herd protection by a bivalent killed whole-cell oral cholera vaccine in the slums of Kolkata, India. Clin Infect Dis. 2013;56(8):1123–1131.
  • Ali M, You YA, Kanungo S, et al. Assessing different measures of population-level vaccine protection using a case-control study. Vaccine. 2015;33(48):6878–6883.
  • DeRoeck D, Clemens JD, Nyamete A, et al. Policymakers’ views regarding the introduction of new-generation vaccines against typhoid fever, shigellosis and cholera in Asia. Vaccine. 2005;23(21):2762–2774.
  • Maskery B, DeRoeck D, Levin A, et al. Strategy, demand, management, and costs of an international cholera vaccine stockpile. J Infect Dis. 2013;208(Suppl 1):S15–22.
  • Henao-Restrepo AM, Longini IM, Egger M, et al. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. Lancet. 2015;386(9996):857–866.
  • Ebola ca Suffit Ring Vaccination Trial C. The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola. BMJ. 2015;351:h3740.
  • Burki T. Ebola virus vaccine receives prequalification. Lancet. 2019;394(10212):1893.
  • WHO. SAGE interim recommendations on vaccination against Ebola Virus Disease (EVD), February 20, 2019. https://www.who.int/immunization/interim_ebola_recommendations_feb_2019.pdf Cited 2022 Mar 11).
  • Hoff NA, Bratcher A, Kelly JD, et al. Immunogenicity of rVSVDeltaG-ZEBOV-GP Ebola vaccination in exposed and potentially exposed persons in the Democratic Republic of the Congo. Proc Natl Acad Sci U S A. 2022;119(6). DOI:10.1073/pnas.2118895119.
  • Ahmed SS, Black S, Ulmer J. New developments and concepts related to biomarker application to vaccines. Microb Biotechnol. 2012;5(2):233–240.
  • Querec TD, Akondy RS, Lee EK, et al. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol. 2009;10(1):116–125.
  • Garcia-Pineres AJ, Hildesheim A, Dodd L, et al. Gene expression patterns induced by HPV-16 L1 virus-like particles in leukocytes from vaccine recipients. J Immunol. 2009;182(3):1706–1729.
  • D’Agostino RB Sr. The delayed-start study design *. N Engl J Med. 2009;361(13):1304–1306.
  • WHO Ad Hoc Expert Group on the Next Steps for Covid-19 Vaccine Evaluation. Krause PR, Fleming TR, Longini, IM, et al. Placebo-controlled trials of covid-19 vaccines - why we still need them. N Engl J Med 2021;384(2):e2.
  • Josefsberg JO, Buckland B. Vaccine process technology. Biotechnol Bioeng. 2012;109(6):1443–1460.
  • Rid A, Saxena A, Baqui AH, et al. Placebo use in vaccine trials: recommendations of a WHO expert panel. Vaccine. 2014;32(37):4708–4712.
  • Deen J, Holmgren J, Clemens J. Evaluating improved inactivated oral cholera vaccines for use in ending endemic cholera by 2030: opportunities and challenges. In preparation).
  • Grenham A, Villafana T. Vaccine development and trials in low and lower-middle income countries: key issues, advances and future opportunities. Hum Vaccin Immunother. 2017;13(9):2192–2199.
  • Alemayehu C, Mitchell G, Nikles J. Barriers for conducting clinical trials in developing countries- a systematic review. Int J Equity Health. 2018;17(1):37.
  • Pilling D. Why medicines must be tested in the developing world. Financial times. London: UK; 2020. [Cited 2022 Mar 12]. Available from: https://www.ft.com/content/501b6857-4272-4f95-9bc6-d47976a59ad6
  • Johnson R, Jackson C, Presanis A, et al. Quantifying efficiency gains of innovative designs of two-arm vaccine trials for COVID-19 using an epidemic simulation model. Stat Biopharm Res. 2022;14(1):33–41.
  • WHO. Handbook for good clinical research practice (‎GCP)‎: guidance for implementation. World Health Organization 2005. https://apps.who.int/iris/handle/10665/43392 Cited 2022 Mar 12).
  • WHO. Guidelines on clinical evaluation of vaccines: regulatory expectations. https://www.who.int/publications/m/item/WHO-TRS-1004-web-annex-9 Accessed on 2022 Aug 23).
  • Hunt A, Saenz C, Littler K. The global forum on bioethics in research meeting, “ethics of alternative clinical trial designs and methods in low- and middle-income country research”: emerging themes and outputs. Trials. 2019;20(Suppl 2):701.

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