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Making the world a simpler place: the modeller’s temptation to seek alternative trial results
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  • Published on:
    Example of a modeller’s temptation to seek alternative trial results
    • Sanne M Thysen, PhD student Bandim Health Project, Guinea-Bissau
    • Other Contributors:
      • Ane B Fisker, Associate Professor
      • Christine S Benn, Professor

    Recently, Colbourn et al questioned the use of modelling to seek alternative trial results1. They cited a radio intervention study from Burkina Faso that based on mathematical modelling suggested that the radio intervention was associated with a 7.1% reduction in under-5 mortality, whereas the actual trial results suggested no effect (Rate ratio: 1.00 (95% CI: 0.82-1.22))1. Colbourn and colleagues raised the important point that modelled estimates should not take precedence over empirical mortality data.
    We would like to support the point raised by Colbourn and colleagues with an example from the field of vaccinology.
    The phase 3 trial of the RTS,S/AS01 malaria vaccine found a vaccine efficacy of 18-36% against clinical malaria2. The study was not powered to assess mortality endpoints, but the results suggested that RTS,S/AS01 was associated with 24% (95% CI: -3 – 58%) higher all-cause mortality3. This was obviously not what was expected; a vaccine that reduces clinical malaria would be expected to reduce all-cause mortality. However, based on our experience, it could indicate that the vaccine, like other non-live vaccines, could have negative non-specific effects4. If that was the case, we predicted that the negative effect would be strongest in females as seen for the other non-live vaccines3. Subsequent analyses indeed revealed that RTS,S/AS01 was associated with higher mortality in girls (Relative Risk of death for RTS,S/AS01 compared with control (RR): 1.9...

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    Conflict of Interest:
    None declared.