Assessing non-inferiority to an aggregate response with an application to development of pneumococcal conjugate vaccines
Article first published online: 9 NOV 2010
Copyright © 2010 John Wiley & Sons, Ltd.
Volume 10, Issue 4, pages 332–340, July/August 2011
How to Cite
Pan, Y., Liu, G. F. and Dallas, M. J. (2011), Assessing non-inferiority to an aggregate response with an application to development of pneumococcal conjugate vaccines. Pharmaceut. Statist., 10: 332–340. doi: 10.1002/pst.470
- Issue published online: 25 JUL 2011
- Article first published online: 9 NOV 2010
- aggregate response;
- conjugate vaccine;
The development of a new pneumococcal conjugate vaccine involves assessing the responses of the new serotypes included in the vaccine. The World Health Organization guidance states that the response from each new serotype in the new vaccine should be compared with the aggregate response from the existing vaccine to evaluate non-inferiority. However, no details are provided on how to define and estimate the aggregate response and what methods to use for non-inferiority comparisons. We investigate several methods to estimate the aggregate response based on binary data including simple average, model-based, and lowest response methods. The response of each new serotype is then compared with the estimated aggregate response for non-inferiority. The non-inferiority test p-value and confidence interval are obtained from Miettinen and Nurminen's method, using an effective sample size. The methods are evaluated using simulations and demonstrated with a real clinical trial example. Copyright © 2010 John Wiley & Sons, Ltd.