I thank the WHO for its response [1] to my article [2].
In its letter, the WHO states that the decision to use randomization in the allocation of malaria vaccine “was taken in conjunction with national authorities as a fair way to allocate limited vaccine doses in the first part of a phased, sub-national introduction. This has the added benefit of strengthening the robustness of the programme evaluation.” [1]
I have not seen any documentation that supports this statement. WHO’s suggestion that the decision to use randomization was driven by a social justice aim of fairness, and not research aims—and therefore just happens to be an added perk that helps strengthen programme evaluation—is at odds with every other WHO document I have reviewed.
Regarding vaccine supply, the WHO’s website says that “GSK is donating up to 10 million doses of RTS,S for use in the pilot programme.” [3] This seems sufficient for a pilot that is vaccinating 360,000 children per year.
Regarding the use of randomization, a 2015 background paper states: “There is a need to evaluate initial introductions before wider scale-up is considered to address a number of issues that remain following the conclusion of the trial. The primary issues are: … The safety signals of most concern (i.e. imbalances in meningitis and cerebral malaria) in the trial may be chance findings, but further evaluation is necessary when the vaccine is given to larger numbers of children” [4]
The document goes on: “It is likely that several hundred thousand vaccinated children will be included in each setting and that phased introduction would need to be randomized to ensure comparability of vaccinated and unvaccinated groups.” [4]
A 2019 policy document similarly outlines the evaluation of “safety signals” as a key reason for the pilot, and states that “the division into vaccine implementation or comparison areas has been completed through randomization to generate the strongest possible evidence on the impact and safety of the vaccine.” [5] The document makes no mention of limited vaccine doses.
[2] Doshi P. WHO’s malaria vaccine study represents a “serious breach of international ethical standards” BMJ 2020;368:m734 https://doi.org/10.1136/bmj.m734 (Published 26 February 2020)
Competing interests:
I authored the article that the WHO has criticized. See https://www.bmj.com/about-bmj/editorial-staff/peter-doshi for a general statement of competing interests.
Rapid Response:
Response from the author
I thank the WHO for its response [1] to my article [2].
In its letter, the WHO states that the decision to use randomization in the allocation of malaria vaccine “was taken in conjunction with national authorities as a fair way to allocate limited vaccine doses in the first part of a phased, sub-national introduction. This has the added benefit of strengthening the robustness of the programme evaluation.” [1]
I have not seen any documentation that supports this statement. WHO’s suggestion that the decision to use randomization was driven by a social justice aim of fairness, and not research aims—and therefore just happens to be an added perk that helps strengthen programme evaluation—is at odds with every other WHO document I have reviewed.
Regarding vaccine supply, the WHO’s website says that “GSK is donating up to 10 million doses of RTS,S for use in the pilot programme.” [3] This seems sufficient for a pilot that is vaccinating 360,000 children per year.
Regarding the use of randomization, a 2015 background paper states: “There is a need to evaluate initial introductions before wider scale-up is considered to address a number of issues that remain following the conclusion of the trial. The primary issues are: … The safety signals of most concern (i.e. imbalances in meningitis and cerebral malaria) in the trial may be chance findings, but further evaluation is necessary when the vaccine is given to larger numbers of children” [4]
The document goes on: “It is likely that several hundred thousand vaccinated children will be included in each setting and that phased introduction would need to be randomized to ensure comparability of vaccinated and unvaccinated groups.” [4]
A 2019 policy document similarly outlines the evaluation of “safety signals” as a key reason for the pilot, and states that “the division into vaccine implementation or comparison areas has been completed through randomization to generate the strongest possible evidence on the impact and safety of the vaccine.” [5] The document makes no mention of limited vaccine doses.
Peter Doshi
References
[1] Swaminathan S, O’Brien K, Alonso P. The WHO Malaria Vaccine Implementation Program: clarifying misconceptions. March 2, 2020. https://www.bmj.com/content/368/bmj.m734/rr-1
[2] Doshi P. WHO’s malaria vaccine study represents a “serious breach of international ethical standards” BMJ 2020;368:m734 https://doi.org/10.1136/bmj.m734 (Published 26 February 2020)
[3] WHO. Q&A on the malaria vaccine implementation programme (MVIP). https://www.who.int/malaria/media/malaria-vaccine-implementation-qa/en/ (March 2020)
[4] Joint Technical Expert Group on Malaria Vaccines (JTEG) And WHO Secretariat. Background paper on the RTS,S/AS01 malaria vaccine. https://www.who.int/immunization/sage/meetings/2015/october/1_Final_mala... (September 2015)
[5] Framework for Policy Decision On RTS,S/AS01 Working Group and the WHO Secretariat. Proposed framework for policy decision on RTS,S/AS01 malaria vaccine. https://www.who.int/immunization/sage/meetings/2019/april/1_Session_7_Fr...(for_print).pdf
(March 13, 2019)
Competing interests: I authored the article that the WHO has criticized. See https://www.bmj.com/about-bmj/editorial-staff/peter-doshi for a general statement of competing interests.