- Email: [email protected]
Is the world ready for an Ebola vaccine?
Comment
The west African Ebola epidemic has motivated efforts to bring an Ebola vaccine to the market as soon as possible. If a candidate vaccine successfully moves through clinical development, a product could be on the market in the next 1–2 years.1–6 Developing an efficacious vaccine will be only part of the process. Post-licensure challenges could impede and even derail an Ebola immunisation programme. We propose seven key challenges to be considered early in Ebola vaccine development that will help stakeholders prepare and allow developers to adjust vaccine characteristics accordingly.7 The first challenge is who will be vaccinated and who will make this decision? Choosing the initial and subsequent target populations for an Ebola vaccine will be complicated, especially if the initial supply of vaccine and data on safety and efficacy are limited and the epidemic continues to evolve. What level of risk will qualify a person or a country to receive an Ebola vaccine? Identification of target areas or groups may necessitate improved surveillance systems and better understanding of Ebola transmission. Second, how will the vaccine reach the target population? Ongoing work has shown that the current immunisation supply chains in low-income and middle-income countries have constraints that impair the flow of many vaccines to their destinations.8,9 These constraints would be further exacerbated by the addition of an Ebola vaccine, which could have unique temperature storage requirements, and by disruptions caused by the Ebola epidemic.10 Ad-hoc mass immunisation campaigns might compensate for some of these shortcomings, but are frequently much more expensive and time and resource intensive than existing supply chains.11 If the target population is large, undertaking a mass immunisation campaign could be difficult. An eventual question is whether an Ebola vaccine should be part of a country’s routine immunisation programme. Mustering adhoc responses to the current epidemic should be accompanied by strengthening affected countries’ current immunisation systems and developing more efficient campaign strategies, including through the use of new methods such as computational simulation modelling which can test the impact of new vaccine designs and technologies.12 www.thelancet.com Vol 385 January 17, 2015
The third challenge concerns how the vaccine will be administered. Successful vaccine administration requires coordination of the vaccine presentation (eg, container size and shape, doses per container, storage requirements, and route of administration); the administration setting and logistics (eg, in a clinic, school, or home); and health-care worker availability, training, and compliance (eg, the more complicated or novel the presentation, the more specialised training, skills, equipment, and immunisation locations need to be). The more costly and scarce a vaccine is, the more important it is to keep vaccine wastage to a minimum. The location and operations of immunisation sites will affect the population’s access to immunisation, the training and recruitment of vaccinators, and information dissemination. Fourth, how safe does the vaccine need to be? Crisis situations should not detract from the need to establish a vaccine’s risk–benefit profile, active safety monitoring, and procedures to address safety concerns, both real and perceived. The scientific community and other stakeholders will have to decide how much to adjust standard regulatory approval processes. Additionally, consideration must be given to the ethics of using a vaccine that might not have been as thoroughly tested as would occur in a noncrisis situation. Any perception that the vaccine is unsafe or not fully tested will impede vaccine acceptance and uptake, especially since the current Ebola outbreak has heightened public mistrust of the health system in some places.13 The fifth challenge involves how the benefits and risks of an Ebola vaccine should be communicated to the public and major stakeholders. A clear vaccine communication plan that addresses both the potential benefits and concerns can help advocates navigate the complex web of stakeholders’ views that will ultimately determine the vaccine programme’s success. Establishing trust will be paramount, especially with accelerated vaccine development and introduction.14 It will be important to align all key stakeholders including governments, suppliers, funders, community leaders, and sectors beyond health care, such as trade and commerce. Different stakeholders have a range of concerns and will respond to various communication
Kenzo Tribouillard/Stringer
Is the world ready for an Ebola vaccine?
See World Report page 214
203
Comment
styles. For all parties, it will be crucial to strike a balance between supporting the vaccine programme while acknowledging any vaccine risks or drawbacks that are either real or perceived. Ebola vaccine development is an opportunity to strengthen public health communications channels and systems in general. A further challenge is how the vaccine would fit into affected countries’ existing fragile health systems. An Ebola vaccine will enter each country’s increasingly complicated health-care ecosystem. The health system must provide the necessary support, which includes delivering and administering the vaccine, distinguishing vaccine side-effects from disease symptoms, maintaining disease surveillance, and implementing other control measures. Health-system decision makers must know what data need to be collected (eg, immunisation records, immunogenicity, efficacy based on confirmed and suspected cases), how data will be analysed, who will undertake the analyses, and how to communicate results. The vaccine’s characteristics could affect collection of these data: if two doses are necessary for protection, how will the country track people who have been immunised and identify and contact those who need a second dose. Moreover, the introduction of an Ebola vaccine could place further strain on existing health and immunisation services for other diseases, which might lead to increased morbidity and outbreaks. The final challenge relates to the cost of an Ebola vaccine and who will pay for it. All these challenges will incur substantial additional cost. Although the Ebola epidemic has momentarily mobilised resources, they will not cover the costs of an entire Ebola vaccine programme and might not be available in the future. New funding mechanisms are therefore needed to make the Ebola vaccine programme sustainable, such as financial incentives for manufacturers and other stakeholders to continue their efforts beyond the current crisis. There are deficiencies in the available economic information and analytical toolkit for new vaccine introductions in general. Informed vaccine decision-making requires clearly documented dynamic strategic demand forecasts, burden estimates, cost-effectiveness, return-on-investment, and budget impact analyses.
204
These challenges require an integrated approach, and will need to be monitored and updated as the Ebola outbreak unfolds. Crisis situations can expose general system deficiencies and ongoing challenges that are otherwise endured. If orchestrated successfully, an Ebola vaccine’s path could serve as a future template for other new vaccines, both emergent and routine, and lead to the overall strengthening of many health systems that are in dire need of improvement. *Bruce Y Lee, William J Moss, Lois Privor-Dumm, Dagna O Constenla, Maria D Knoll, Katherine L O’Brien International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA [email protected] We declare no competing interests. BYL is a member of the Hopkins Ebola Africa Response Consortium and an investigator for the MIDAS Informatics Service Group, supported by the National Institute of General Medical Sciences/National Institutes of Health. KLO’B is a member of WHO’s Strategic Advisory Group of Experts. 1
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WHO. WHO convenes industry leaders and key partners to discuss trials and production of ebola vaccines. Oct 24, 2014. http://www.who.int/ mediacentre/news/releases/2014/ebola-vaccines-production/en/ (accessed Dec 19, 2014). Bishop BM. Potential and emerging treatment options for Ebola virus disease. Ann Pharmacother 2014; published online Nov 20. pii: 1060028014561227. Gulland A. Vaccine tests to begin in Ebola countries this year. BMJ 2014; 349: g6466. Kanapathipillai R, Restrepo AMH, Fast P, et al. Ebola vaccine—an urgent international priority. N Engl J Med 2014; 371: 2249–51. Ledgerwood JE, DeZure AD, Stanley DA, et al. Chimpanzee adenovirus vector Ebola vaccine—preliminary report. N Engl J Med 2014; published online Nov 26. DOI: 10.1056/NEJMoa1410863. Mire CE, Geisbert JB, Marzi A, Agans KN, Feldmann H, Geisbert TW. Vesicular stomatitis virus-based vaccines protect nonhuman primates against Bundibugyo ebolavirus. PLoS Negl Trop Dis 2013; 7: e2600. Lee BY, Burke DS. Constructing target product profiles (TPPs) to help vaccines overcome post-approval obstacles. Vaccine 2010; 28: 2806–09. Brown ST, Schreiber B, Cakouros BE, et al. The benefits of redesigning Benin’s vaccine supply chain. Vaccine 2014; 32: 4097–103. Lee BY, Assi TM, Rajgopal J, et al. Impact of introducing the pneumococcal and rotavirus vaccines into the routine immunization program in Niger. Am J Public Health 2012; 102: 269–76. WHO. Experimental Ebola vaccines. 2014. http://www.who.int/ mediacentre/news/ebola/01-october-2014/en/index1.html (accessed Dec 1, 2014). Doumtsop JG, Malano ER, Diallo IT, Sirimah C. An evaluation of the 2012 measles mass vaccination campaign in Guinea. Pan Afr Med J 2014; 8: 4. Lee BY, Cakouros BE, Assi TM, et al. The impact of making vaccines thermostable in Niger’s vaccine supply chain. Vaccine 2012; 30: 5637–43. Gounder C. To combat Ebola, first build back trust in healthcare workers. Reuters July 30, 2014. http://blogs.reuters.com/great-debate/2014/07/30/ efforts-against-ebola-outbreak-hampered-by-victims-lack-of-trust-inhealthcare-workers/ (accessed Jan 12, 2014). Freimuth VS, Musa D, Hilyard K, Quinn SC, Kim K. Trust during the early stages of the 2009 H1N1 pandemic. J Health Commun 2014; 19: 321–39.
www.thelancet.com Vol 385 January 17, 2015
The west African Ebola epidemic has motivated efforts to bring an Ebola vaccine to the market as soon as possible. If a candidate vaccine successfully moves through clinical development, a product could be on the market in the next 1–2 years.1–6 Developing an efficacious vaccine will be only part of the process. Post-licensure challenges could impede and even derail an Ebola immunisation programme. We propose seven key challenges to be considered early in Ebola vaccine development that will help stakeholders prepare and allow developers to adjust vaccine characteristics accordingly.7 The first challenge is who will be vaccinated and who will make this decision? Choosing the initial and subsequent target populations for an Ebola vaccine will be complicated, especially if the initial supply of vaccine and data on safety and efficacy are limited and the epidemic continues to evolve. What level of risk will qualify a person or a country to receive an Ebola vaccine? Identification of target areas or groups may necessitate improved surveillance systems and better understanding of Ebola transmission. Second, how will the vaccine reach the target population? Ongoing work has shown that the current immunisation supply chains in low-income and middle-income countries have constraints that impair the flow of many vaccines to their destinations.8,9 These constraints would be further exacerbated by the addition of an Ebola vaccine, which could have unique temperature storage requirements, and by disruptions caused by the Ebola epidemic.10 Ad-hoc mass immunisation campaigns might compensate for some of these shortcomings, but are frequently much more expensive and time and resource intensive than existing supply chains.11 If the target population is large, undertaking a mass immunisation campaign could be difficult. An eventual question is whether an Ebola vaccine should be part of a country’s routine immunisation programme. Mustering adhoc responses to the current epidemic should be accompanied by strengthening affected countries’ current immunisation systems and developing more efficient campaign strategies, including through the use of new methods such as computational simulation modelling which can test the impact of new vaccine designs and technologies.12 www.thelancet.com Vol 385 January 17, 2015
The third challenge concerns how the vaccine will be administered. Successful vaccine administration requires coordination of the vaccine presentation (eg, container size and shape, doses per container, storage requirements, and route of administration); the administration setting and logistics (eg, in a clinic, school, or home); and health-care worker availability, training, and compliance (eg, the more complicated or novel the presentation, the more specialised training, skills, equipment, and immunisation locations need to be). The more costly and scarce a vaccine is, the more important it is to keep vaccine wastage to a minimum. The location and operations of immunisation sites will affect the population’s access to immunisation, the training and recruitment of vaccinators, and information dissemination. Fourth, how safe does the vaccine need to be? Crisis situations should not detract from the need to establish a vaccine’s risk–benefit profile, active safety monitoring, and procedures to address safety concerns, both real and perceived. The scientific community and other stakeholders will have to decide how much to adjust standard regulatory approval processes. Additionally, consideration must be given to the ethics of using a vaccine that might not have been as thoroughly tested as would occur in a noncrisis situation. Any perception that the vaccine is unsafe or not fully tested will impede vaccine acceptance and uptake, especially since the current Ebola outbreak has heightened public mistrust of the health system in some places.13 The fifth challenge involves how the benefits and risks of an Ebola vaccine should be communicated to the public and major stakeholders. A clear vaccine communication plan that addresses both the potential benefits and concerns can help advocates navigate the complex web of stakeholders’ views that will ultimately determine the vaccine programme’s success. Establishing trust will be paramount, especially with accelerated vaccine development and introduction.14 It will be important to align all key stakeholders including governments, suppliers, funders, community leaders, and sectors beyond health care, such as trade and commerce. Different stakeholders have a range of concerns and will respond to various communication
Kenzo Tribouillard/Stringer
Is the world ready for an Ebola vaccine?
See World Report page 214
203
Comment
styles. For all parties, it will be crucial to strike a balance between supporting the vaccine programme while acknowledging any vaccine risks or drawbacks that are either real or perceived. Ebola vaccine development is an opportunity to strengthen public health communications channels and systems in general. A further challenge is how the vaccine would fit into affected countries’ existing fragile health systems. An Ebola vaccine will enter each country’s increasingly complicated health-care ecosystem. The health system must provide the necessary support, which includes delivering and administering the vaccine, distinguishing vaccine side-effects from disease symptoms, maintaining disease surveillance, and implementing other control measures. Health-system decision makers must know what data need to be collected (eg, immunisation records, immunogenicity, efficacy based on confirmed and suspected cases), how data will be analysed, who will undertake the analyses, and how to communicate results. The vaccine’s characteristics could affect collection of these data: if two doses are necessary for protection, how will the country track people who have been immunised and identify and contact those who need a second dose. Moreover, the introduction of an Ebola vaccine could place further strain on existing health and immunisation services for other diseases, which might lead to increased morbidity and outbreaks. The final challenge relates to the cost of an Ebola vaccine and who will pay for it. All these challenges will incur substantial additional cost. Although the Ebola epidemic has momentarily mobilised resources, they will not cover the costs of an entire Ebola vaccine programme and might not be available in the future. New funding mechanisms are therefore needed to make the Ebola vaccine programme sustainable, such as financial incentives for manufacturers and other stakeholders to continue their efforts beyond the current crisis. There are deficiencies in the available economic information and analytical toolkit for new vaccine introductions in general. Informed vaccine decision-making requires clearly documented dynamic strategic demand forecasts, burden estimates, cost-effectiveness, return-on-investment, and budget impact analyses.
204
These challenges require an integrated approach, and will need to be monitored and updated as the Ebola outbreak unfolds. Crisis situations can expose general system deficiencies and ongoing challenges that are otherwise endured. If orchestrated successfully, an Ebola vaccine’s path could serve as a future template for other new vaccines, both emergent and routine, and lead to the overall strengthening of many health systems that are in dire need of improvement. *Bruce Y Lee, William J Moss, Lois Privor-Dumm, Dagna O Constenla, Maria D Knoll, Katherine L O’Brien International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA [email protected] We declare no competing interests. BYL is a member of the Hopkins Ebola Africa Response Consortium and an investigator for the MIDAS Informatics Service Group, supported by the National Institute of General Medical Sciences/National Institutes of Health. KLO’B is a member of WHO’s Strategic Advisory Group of Experts. 1
2
3 4 5
6
7 8 9
10
11 12 13
14
WHO. WHO convenes industry leaders and key partners to discuss trials and production of ebola vaccines. Oct 24, 2014. http://www.who.int/ mediacentre/news/releases/2014/ebola-vaccines-production/en/ (accessed Dec 19, 2014). Bishop BM. Potential and emerging treatment options for Ebola virus disease. Ann Pharmacother 2014; published online Nov 20. pii: 1060028014561227. Gulland A. Vaccine tests to begin in Ebola countries this year. BMJ 2014; 349: g6466. Kanapathipillai R, Restrepo AMH, Fast P, et al. Ebola vaccine—an urgent international priority. N Engl J Med 2014; 371: 2249–51. Ledgerwood JE, DeZure AD, Stanley DA, et al. Chimpanzee adenovirus vector Ebola vaccine—preliminary report. N Engl J Med 2014; published online Nov 26. DOI: 10.1056/NEJMoa1410863. Mire CE, Geisbert JB, Marzi A, Agans KN, Feldmann H, Geisbert TW. Vesicular stomatitis virus-based vaccines protect nonhuman primates against Bundibugyo ebolavirus. PLoS Negl Trop Dis 2013; 7: e2600. Lee BY, Burke DS. Constructing target product profiles (TPPs) to help vaccines overcome post-approval obstacles. Vaccine 2010; 28: 2806–09. Brown ST, Schreiber B, Cakouros BE, et al. The benefits of redesigning Benin’s vaccine supply chain. Vaccine 2014; 32: 4097–103. Lee BY, Assi TM, Rajgopal J, et al. Impact of introducing the pneumococcal and rotavirus vaccines into the routine immunization program in Niger. Am J Public Health 2012; 102: 269–76. WHO. Experimental Ebola vaccines. 2014. http://www.who.int/ mediacentre/news/ebola/01-october-2014/en/index1.html (accessed Dec 1, 2014). Doumtsop JG, Malano ER, Diallo IT, Sirimah C. An evaluation of the 2012 measles mass vaccination campaign in Guinea. Pan Afr Med J 2014; 8: 4. Lee BY, Cakouros BE, Assi TM, et al. The impact of making vaccines thermostable in Niger’s vaccine supply chain. Vaccine 2012; 30: 5637–43. Gounder C. To combat Ebola, first build back trust in healthcare workers. Reuters July 30, 2014. http://blogs.reuters.com/great-debate/2014/07/30/ efforts-against-ebola-outbreak-hampered-by-victims-lack-of-trust-inhealthcare-workers/ (accessed Jan 12, 2014). Freimuth VS, Musa D, Hilyard K, Quinn SC, Kim K. Trust during the early stages of the 2009 H1N1 pandemic. J Health Commun 2014; 19: 321–39.
www.thelancet.com Vol 385 January 17, 2015