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. 2022 Apr 25;21(1):132.
doi: 10.1186/s12936-022-04144-3.

Assessing the safety, impact and effectiveness of RTS,S/AS01E malaria vaccine following its introduction in three sub-Saharan African countries: methodological approaches and study set-up

Nicolas Praet  1   2 , Kwaku Poku Asante  3   4 , Marie-Cecile Bozonnat  5 , Elaine Jacqueline Akité  6 , Patrick Odum Ansah  7 , Laurence Baril  8 , Owusu Boahen  3 , Yolanda Guerra Mendoza  6 , Valerie Haine  6 , Simon Kariuki  9 , Mathieu Lamy  10 , Kenneth Maleta  11 , Randy Mungwira  11 , Latif Ndeketa  12 , Abraham Oduro  7 , Bernhards Ogutu  13   14 , Fredrick Olewe  13 , Martina Oneko  9 , Mattéa Orsini  5 , Francois Roman  6 , Edith Roset Bahmanyar  15 , Dominique Rosillon  6   16 , Lode Schuerman  6 , Valentine Sing'oei  17 , Dianne J Terlouw  12   18 , Stéphanie Wéry  6 , Walter Otieno  17 , Jean-Yves Pirçon  6
Affiliations

Assessing the safety, impact and effectiveness of RTS,S/AS01E malaria vaccine following its introduction in three sub-Saharan African countries: methodological approaches and study set-up

Nicolas Praet et al. Malar J. .

Abstract

Background: Following a 30-year development process, RTS,S/AS01E (GSK, Belgium) is the first malaria vaccine to reach Phase IV assessments. The World Health Organization-commissioned Malaria Vaccine Implementation Programme (MVIP) is coordinating the delivery of RTS,S/AS01E through routine national immunization programmes in areas of 3 countries in sub-Saharan Africa. The first doses were given in the participating MVIP areas in Malawi on 23 April, Ghana on 30 April, and Kenya on 13 September 2019. The countries participating in the MVIP have little or no baseline incidence data on rare diseases, some of which may be associated with immunization, a deficit that could compromise the interpretation of possible adverse events reported following the introduction of a new vaccine in the paediatric population. Further, effects of vaccination on malaria transmission, existing malaria control strategies, and possible vaccine-mediated selective pressure on Plasmodium falciparum variants, could also impact long-term malaria control. To address this data gap and as part of its post-approval commitments, GSK has developed a post-approval plan comprising of 4 complementary Phase IV studies that will evaluate safety, effectiveness and impact of RTS,S/AS01E through active participant follow-up in the context of its real-life implementation.

Methods: EPI-MAL-002 (NCT02374450) is a pre-implementation safety surveillance study that is establishing the background incidence rates of protocol-defined adverse events of special interest. EPI-MAL-003 (NCT03855995) is an identically designed post-implementation safety and vaccine impact study. EPI-MAL-005 (NCT02251704) is a cross-sectional pre- and post-implementation study to measure malaria transmission intensity and monitor the use of other malaria control interventions in the study areas, and EPI-MAL-010 (EUPAS42948) will evaluate the P. falciparum genetic diversity in the periods before and after vaccine implementation.

Conclusion: GSK's post-approval plan has been designed to address important knowledge gaps in RTS,S/AS01E vaccine safety, effectiveness and impact. The studies are currently being conducted in the MVIP areas. Their implementation has provided opportunities and posed challenges linked to conducting large studies in regions where healthcare infrastructure is limited. The results from these studies will support ongoing evaluation of RTS,S/AS01E's benefit-risk and inform decision-making for its potential wider implementation across sub-Saharan Africa.

Keywords: Effectiveness; Impact; Malaria; Plasmodium falciparum; Protocol; RTS,S/AS01E; Safety.

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Conflict of interest statement

EJA, YGM, VH, FR, LS, SW and JYP are employees of the GSK group of companies. At the time of the study NP was an employee of the GSK group of companies and is now employed by Janssen Pharmaceutica NV. At the time of the study DR was an employee of the GSK group of companies and is now a freelance consultant at DESiRE-Consulting. NP, YGM, ML, FR, LS, DR and JYP hold shares in the GSK group of companies. ML is employee of Aixial on behalf of the GSK group of companies. MOr and MCB are employees of 4Clinics on behalf of the GSK group of companies. KPA, POA, OB, SK, KM, RM, LN, AO, BO, FO, MOn, VS, DJT and WO via their institutions, received grants from the GSK group of companies for the conduct of this study/work. KPA, OB, SK, WO, VS, KM and DJT via their institutions, received grants from the GSK group of companies for the conduct of studies outside the submitted work.

Figures

Fig. 1
Fig. 1
Overview GSK’s RTS,S/AS01E vaccine post-approval plan embedded within the Malaria Vaccine Implementation Programme. AESIs adverse events of special interest, LSLV last subject last visit, MoH Ministry of Health, MVPE Malaria Vaccine Programme Evaluation, WHO World Health Organization, NRA National Regulatory Authority
Fig. 2
Fig. 2
Evaluation of safety, effectiveness and impact using data collected as part of the RTS,S/AS01E post-approval plan. AESI adverse events of special interest. Asterisk indicates the potential risk of meningitis will be monitored on ongoing basis using the maximized sequential probability ratio test (MaxSPRT) method
See this image and copyright information in PMC

References

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