Serra, Alessandra, Mozgunov, Pavel, Davies, Geraint 
ORCID: 0000-0002-3819-490X and Jaki, Thomas
(2023)
Determining the minimum duration of treatment in tuberculosis: An order restricted non-inferiority trial design.
PHARMACEUTICAL STATISTICS, 22 (5).
pp. 938-962.
Abstract
Tuberculosis (TB) is one of the biggest killers among infectious diseases worldwide. Together with the identification of drugs that can provide benefits to patients, the challenge in TB is also the optimisation of the duration of these treatments. While conventional duration of treatment in TB is 6 months, there is evidence that shorter durations might be as effective but could be associated with fewer side effects and may be associated with better adherence. Based on a recent proposal of an adaptive order-restricted superiority design that employs the ordering assumptions within various duration of the same drug, we propose a non-inferiority (typically used in TB trials) adaptive design that effectively uses the order assumption. Together with the general construction of the hypothesis testing and expression for type I and type II errors, we focus on how the novel design was proposed for a TB trial concept. We consider a number of practical aspects such as choice of the design parameters, randomisation ratios, and timings of the interim analyses, and how these were discussed with the clinical team.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | adaptive designs, infectious diseases, multi-arm multi-stage, non-inferiority, order restriction |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 03 Oct 2023 08:41 |
| Last Modified: | 03 Oct 2023 08:42 |
| DOI: | 10.1002/pst.2320 |
| Open Access URL: | https://doi.org/10.1002/pst.2320 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3173345 |
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