Sample size considerations using mathematical models: an example with Chlamydia trachomatis infection and its sequelae pelvic inflammatory disease

BMC Infectious Diseases

Research Article

Sereina A Herzog¹  Andrea Berghold¹  Nicola Low² 

[1] Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria;Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland;

关键词: Sample size calculation;    Mathematical model;    Compartmental model;    Randomised controlled trials;    Chlamydia infection;    Pelvic inflammatory disease;   

DOI  :  10.1186/s12879-015-0953-5

 received in 2015-01-12, accepted in 2015-05-19,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe success of an intervention to prevent the complications of an infection is influenced by the natural history of the infection. Assumptions about the temporal relationship between infection and the development of sequelae can affect the predicted effect size of an intervention and the sample size calculation. This study investigates how a mathematical model can be used to inform sample size calculations for a randomised controlled trial (RCT) using the example of Chlamydia trachomatis infection and pelvic inflammatory disease (PID).MethodsWe used a compartmental model to imitate the structure of a published RCT. We considered three different processes for the timing of PID development, in relation to the initial C. trachomatis infection: immediate, constant throughout, or at the end of the infectious period. For each process we assumed that, of all women infected, the same fraction would develop PID in the absence of an intervention. We examined two sets of assumptions used to calculate the sample size in a published RCT that investigated the effect of chlamydia screening on PID incidence. We also investigated the influence of the natural history parameters of chlamydia on the required sample size.ResultsThe assumed event rates and effect sizes used for the sample size calculation implicitly determined the temporal relationship between chlamydia infection and PID in the model. Even small changes in the assumed PID incidence and relative risk (RR) led to considerable differences in the hypothesised mechanism of PID development. The RR and the sample size needed per group also depend on the natural history parameters of chlamydia.ConclusionsMathematical modelling helps to understand the temporal relationship between an infection and its sequelae and can show how uncertainties about natural history parameters affect sample size calculations when planning a RCT.

【 授权许可】

CC BY   
© Herzog et al. 2015

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