Responses

PDF

Making the world a simpler place: the modeller’s temptation to seek alternative trial results
Compose Response

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Statement of Competing Interests

PLEASE NOTE:

  • Responses are moderated before posting and publication is at the absolute discretion of BMJ, however they are not peer-reviewed
  • Once published, you will not have the right to remove or edit your response. Removal or editing of responses is at BMJ's absolute discretion
  • If patients could recognise themselves, or anyone else could recognise a patient from your description, please obtain the patient's written consent to publication and send them to the editorial office before submitting your response [Patient consent forms]
  • By submitting this response you are agreeing to our full [Response terms and requirements]

Vertical Tabs

Other responses

Jump to comment:

  • 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...

    Show More
    Conflict of Interest:
    None declared.