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BMJ. Author manuscript; available in PMC 2012 February 27.
Published in final edited form as:
PMCID: PMC3287289
EMSID: UKMS41050

What is the efficacy of RTS,S?

Christopher J.A. Duncan, Research Fellow1 and Adrian V.S. Hill, Professor1

Whitty’s insightful editorial 1 puts the recent phase III RTS,S malaria vaccine trial results 2 in the wider context of malaria control. While vaccines are an important potential component of this effort, they are not necessarily the complete solution. RTS,S is clearly a big step in the right direction, although further advances are needed towards the goal of a highly effective malaria vaccine. 1

The decision to publish interim efficacy data from an ongoing phase III study is unusual, 3 and others have questioned the headline efficacy figure of around 50% in time to first malaria episode. 4 Efficacy estimates will critically influence decisions on the public health role for RTS,S, and we wish to clarify some aspects of the published analysis.

A readily interpretable method of vaccine efficacy analysis involves calculating the risk ratio (the proportion of malaria in the intervention group over the control group). 5 Using this approach efficacy against clinical malaria in older children is more modest at 34% (intention-to-treat) or 36% (per-protocol).

RTS,S is thought to reduce the risk of infection from each exposure, rather than conferring “all or nothing” protection on a proportion of recipients. 5 By this hypothesis, everyone vaccinated will eventually experience malaria if transmission is high enough. 5 In other words, the vaccine should have a greater effect on the incidence rate of the first or total episodes of clinical malaria than on the overall proportion of people experiencing it, a conclusion supported by the phase III data. 2 While analysis of hazard and incidence rate ratios are completely valid 5, the risk ratio for clinical malaria provides additional highly relevant information to both policy makers and parents of immunised children, and should also be reported.

Footnotes

Conflict of Interest: AVSH is a named inventor on patent applications covering malaria vectored vaccines and immunisation regimes.

References

1. Whitty CJ. The RTS,S malaria vaccine. Bmj. 2011;343:d6986. [PubMed]
2. First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children. The New England journal of medicine. 2011 [PubMed]
3. White NJ. A Vaccine for Malaria. The New England journal of medicine. 2011 [PubMed]
4. Butler D. Malaria vaccine results face scrutiny. Nature. 2011;478(7370):439–40. [PubMed]
5. Lievens M, Aponte JJ, Williamson J, Mmbando B, Mohamed A, Bejon P, et al. Statistical methodology for the evaluation of vaccine efficacy in a phase III multi-centre trial of the RTS, S/AS01 malaria vaccine in African children. Malar J. 2011;10:222. [PMC free article] [PubMed]