Efficacy and Safety of RTS,S/AS01 Malaria Vaccine with or without a Booster Dose in Infants and Children in Africa
2015 · paper · Clinical trials
Reports final results of a phase 3 trial of the RTS,S/AS01 malaria vaccine in African infants and children, with or without a booster dose. The provided text covers the trial design and not the findings.
Checked: PDF from europepmc.org, fetched 4 Oct 2026. Page numbers are those of that PDF.
6 findings
Substance Table 3 footnote ‡ gives the median follow-up as "39 months after the first dose for the 6–12 weeks age category", whereas the abstract ("38 months (34–41)"), Methods ("38 months for young infants"), Results ("median overall 37·7 months") and Figure 6 title ("38 months of follow-up") give 38.
- p. 28 Table 3 footnote ‡
39 months after the first dose for the 6–12 weeks age category
- p. 2 Summary, Findings
infants for 38 months (34–41) after dose 1
- p. 6 Results, first paragraph
median overall 37·7 months
- p. 23 Figure 6 title
during 38 months of follow-up
Judge's note: Viewed the page 28 image: the footnote says 39 months. Text lines 64, 124, 262–263 and 818 give 38 or 37·7 months (per-group medians 37·8, 37·7, 37·8), all modified ITT and all after dose 1. No different population or measure is described for Table 3, which is also modified ITT. The same Results sentence also has unbalanced brackets: '(median overall 37·7 months, (IQR 34·1–41·1; modified ITT)', a separate cosmetic point.
Second check: another model agreed
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Substance Figure 3A 'Overall' row prints "28·2 (23·3–32·9)" while Table 1, the Results text and the abstract give "28·3%" with the same interval (23·3 to 32·9) for the same analysis.
- p. 20 Figure 3A, 'Overall' row
28·2 (23·3–32·9)
- p. 25 Table 1, 5–17 months, Month 0 to study end, R3C vs C3C
28·3%
- p. 6 Results, second paragraph
the R3C group (28·3%, 23·3–32·9
- p. 20 Figure 3A, Overall row
28·2 (23·3 to 32·9)
Judge's note: Viewed the page 20 image: the Figure 3A Overall row reads 28·2 (23·3–32·9). Table 1 (page 25) gives 28·3% (23·3 to 32·9) for 5–17 months, month 0 to study end, R3C vs C3C; text lines on pages 2 and 6 give 28·3%. The figure caption states modified ITT, month 0 to study end, primary case definition, the same as Table 1, and the interval is identical; Figure 3B's 36·3 matches the table. No explanation found in the text. The difference is 0·1 percentage point; the figure digit was read from the page image at its available resolution.
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Substance Figure 5A, Kilifi, Kenya row prints "23·1 (117·5 to 72·8)": the lower bound lacks its minus sign, so it exceeds both the point estimate and the upper bound.
- p. 22 Figure 5A, Kilifi, Kenya row
23·1 (117·5 to 72·8)
Judge's note: Viewed the page 22 image. The Kilifi row in panel A reads 23·1 (117·5 to 72·8), while other rows in the same panel show minus signs (e.g. –41·6, –106·0). The plotted bar has an arrow running off the left of the axis (below –100), so the bound is evidently –117·5. The bounds are in the wrong order as printed.
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Reference or label Reference 18 ("Kester K, Cummings J, Ofori-Anyinam O, et al. Randomized, double-blind, phase 2a trial of falciparum malaria vaccines RTS,S/AS01B and RTS,S/AS02A in malaria-naive adults ... J Infect Dis. 2009; 200:337–46. [PubMed: 19569965]") is the same entry as reference 4, and is cited for "limited data from a previous study18 suggest that the antibody response to a booster dose in children who had been primed with RTS,S/AS01".
- p. 11 Discussion, paragraph on anti-circumsporozoite titres
limited data from a previous study18 suggest that the antibody response to a booster dose in children who had been primed with RTS,S/AS01
- p. 14 Reference 18
Kester K, Cummings J, Ofori-Anyinam O, et al. Randomized, double-blind, phase 2a trial of falciparum malaria vaccines RTS,S/AS01B and RTS,S/AS02A in malaria-naive adults
- p. 13 Reference 4
Kester KE, Cummings JF, Ofori-Anyinam O, et al. Randomized, double-blind, phase 2a trial of
- p. 11 Discussion, paragraph 3
limited data from a previous study18 suggest that the antibody response to a booster dose in children who had been primed with RTS,S/AS01 was greater than that reported in participants who had received a single dose without priming
Only the authors can say what is right here.
Judge's note: Read reference lists on pages 13 and 14 and the Discussion on page 11. References 4 and 18 have the same title, journal, year, volume, pages and PubMed ID; only the author initials differ. So the duplication is certain from the files. The title of the entry concerns malaria-naive adults while the citing sentence concerns primed children; only the authors can say which source was intended.
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Reference or label Table 3 footnote markers are misplaced: the case-definition footnote '*' is attached to the row label "Months 0–20*" under severe malaria, fatal malaria, all-cause hospital admission, all-cause mortality, incident severe anaemia and blood transfusion (but not under clinical malaria or malaria hospital admission), and the final "Month 0 to study end" row under Blood transfusion lacks the ‡ carried by every other such row.
- p. 27 Table 3, row labels under Severe malaria, Fatal malaria, All-cause hospital admission, All-cause mortality, Incident severe anaemia
Months 0–20*
- p. 28 Table 3 (continued), Blood transfusion
Month 0 to study end
- p. 28 Table 3 footnote *
This definition was used for this analysis because, during routine clinical practice
Judge's note: Viewed pages 27 and 28. Footnote * reads 'This definition was used for this analysis because...' and is attached to the heading 'Clinical malaria (secondary case definition)*', where it fits. It also appears on 'Months 0–20*' under six outcomes, including ones with no case-definition choice, and is absent from the 'Severe malaria (secondary case definition)' heading. On page 28 the Blood transfusion row 'Month 0 to study end' has no ‡ although the ‡ footnote is printed beneath. The data are unaffected.
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Wording "RTS,S/AS01 might have reduced the numbers of cases averted of these endpoints even more in communities where access to a high level of clinical care is less readily accessible" says the reverse of the argument being made (a larger benefit where care is poorer); the sense needed is 'reduced the numbers of cases' or 'increased the numbers of cases averted'.
- p. 11 Discussion, first paragraph on the page
RTS,S/AS01 might have reduced the numbers of cases averted of these endpoints even more in communities
- p. 11 Discussion, paragraph 2 (continued), top of page
RTS,S/AS01 might have reduced the numbers of cases averted of these endpoints even more in communities where access to a high level of clinical care is less readily accessible
- p. 11 Discussion, same paragraph, two sentences earlier
Failure to detect an effect of RTS,S/AS01 on these secondary outcomes, including mortality, might have been caused in part by the high level of clinical care provided during the trial
Judge's note: Read page 11 image. The preceding sentence attributes failure to detect an effect partly to the high level of care in the trial, so the argument is for a larger benefit elsewhere. As printed, 'reduced the numbers of cases averted' means a smaller benefit. A wording slip; 'access ... is less readily accessible' is also redundant.
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8 minor (typos and the like; most checked by the judge only)
Wording Discussion: "The decrease in efficacy of RTS,S/AS01 against clinical and severe malaria over time ... continued during the extended follow-up period in both children and infants who did not receive a booster dose"; for severe malaria in infants, Table 2 R3C vs C3C shows 8·3% (months 0–20, pooled), 7·9% (months 21–32) and "12·6% (–91·2 to 60·5)" (month 33 to study end), with no declining pattern.
- p. 10 Discussion, first sentence
The decrease in efficacy of RTS,S/AS01 against clinical and severe malaria over time since vaccination, which was reported previously,9 continued during the extended follow-up period in both children and infants who did not receive a booster dose of vaccine.
- p. 26 Table 2, 6–12 weeks age category, R3C vs C3C, Months 0–20
8·3% (–25·7 to 32·6)
- p. 26 Table 2, 6–12 weeks age category, R3C vs C3C, Month 33 to study end
12·6% (–91·2 to 60·5)
Judge's note: Read Table 2 on the upright page 26 image; the three infant values are as quoted, and the months 0–20 row is the pooled R3R plus R3C comparison (footnote †). For children the severe malaria estimates do fall (33·9%, –44·4%, –57·9%), and the clinical malaria statement is consistent with the text. All infant severe-malaria intervals are wide and include zero, so this is a loose generalisation.
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Typo Singular 'p' used with page ranges: "(appendix p 74–76)", "(appendix p 88–90)", "(appendix p 44–45)" (also "appendix p 92–93"), whereas other ranges use 'pp' (e.g. "appendix pp 72–73").
- p. 7 Results, severe anaemia/hospital admission
(appendix p 74–76)
- p. 8 Results, young infants
(appendix p 88–90)
- p. 3 Methods
(appendix p 44–45)
Judge's note: Checked on page images 3, 7 and 8. All three quoted instances are printed as stated, and the paper elsewhere uses 'pp' for ranges. Cosmetic style inconsistency.
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Typo Stray, unclosed opening parenthesis: "(median overall 37·7 months, (IQR 34·1–41·1; modified ITT)"; the parallel sentence reads "(median overall 48·2 months, IQR 39·4–50·1; modified ITT)".
- p. 6 Results, first paragraph
(median overall 37·7 months, (IQR 34·1–41·1; modified ITT)
Judge's note: Seen on the crop of page 6: the second '(' before IQR is present in the image and is never closed.
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Typo Plural 'pp' with a single page: "(appendix pp 88)"; two lines later the same page is cited as "(appendix p 88)".
- p. 8 Results, severe malaria anaemia, young infants
(appendix pp 88)
Judge's note: Seen on page 8 image, severe malaria anaemia sentence for young infants. Either a typo for 'p 88' or a truncated range; cosmetic.
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Typo The same journal is abbreviated two ways: reference 3 "Hum Vacc. 2010; 6:90–96." and reference 17 "Hum Vaccin. 2009; 5:242–47."
- p. 13 Reference 3
Hum Vacc. 2010; 6:90–96.
- p. 14 Reference 17
Hum Vaccin. 2009; 5:242–47.
Judge's note: Seen on pages 13 and 14 images. Purely a style inconsistency in the reference list; reference 3 also writes the page range in full where others abbreviate.
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Typo Reference 13 access date printed with a truncated year: "[accessed April 22, 015]"; reference 19 has "[accessed April 22, 2015]".
- p. 14 Reference 13
[accessed April 22, 015]
Judge's note: Confirmed on the page 14 image; the year is printed '015', so it is not an extraction artefact.
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Typo Figure 2 (participants aged 6–12 weeks) footnote reads "†2115 children in the with booster group, 2119 in the without booster group", although the same legend says "*For 118 infants" and the paper calls this cohort infants.
- p. 18 Figure 2 footnote †
†2115 children in the with booster group, 2119 in the without booster group
- p. 18 Figure 2 footnote †
†2115 children in the with booster group
Judge's note: Seen on the crop of page 18. The footnote uses 'children' for the infant cohort while the preceding footnote in the same legend uses 'infants'. It appears to be carried over from the Figure 1 legend; minor terminology slip.
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Typo Table 1 last column header reads "Incremental eficacy"; should be "Incremental efficacy".
- p. 25 Table 1, last column header
Incremental eficacy
Judge's note: Viewed the page 25 upright image: the header is printed 'Incremental eficacy unadjusted for covariates R3R vs R3C'. The table caption spells 'efficacy' correctly. Also present in the text layer (line 854).
Second check: none (judge only)