| Title: |
The use of randomisation-based efficacy estimators in non-inferiority trials |
| Authors: |
Gillespie, David; Farewell, Daniel; Barrett-Lee, Peter; Casbard, Angela; Hawthorne, Anthony Barney; Hurt, Chris; Murray, Nick; Probert, Chris; Stenson, Rachel; Hood, Kerenza |
| Publication Year: |
2017 |
| Collection: |
University of Southampton: e-Prints Soton |
| Description: |
Background: in a non-inferiority (NI) trial, analysis based on the intention-to-treat (ITT) principle is anti-conservative, so current guidelines recommend analysing on a per-protocol (PP) population in addition. However, PP analysis relies on the often implausible assumption of no confounders. Randomisation-based efficacy estimators (RBEEs) allow for treatment non-adherence while maintaining a comparison of randomised groups. Fischer et al. have developed an approach for estimating RBEEs in randomised trials with two active treatments, a common feature of NI trials. The aim of this paper was to demonstrate the use of RBEEs in NI trials using this approach, and to appraise the feasibility of these estimators as the primary analysis in NI trials. Methods: two NI trials were used. One comparing two different dosing regimens for the maintenance of remission in people with ulcerative colitis (CODA), and the other comparing an orally administered treatment to an intravenously administered treatment in preventing skeletal-related events in patients with bone metastases from breast cancer (ZICE). Variables that predicted adherence in each of the trial arms, and were also independent of outcome, were sought in each of the studies. Structural mean models (SMMs) were fitted that conditioned on these variables, and the point estimates and confidence intervals compared to that found in the corresponding ITT and PP analyses. Results: in the CODA study, no variables were found that differentially predicted treatment adherence while remaining independent of outcome. The SMM, using standard methodology, moved the point estimate closer to 0 (no difference between arms) compared to the ITT and PP analyses, but the confidence interval was still within the NI margin, indicating that the conclusions drawn would remain the same. In the ZICE study, cognitive functioning as measured by the corresponding domain of the QLQ-C30, and use of chemotherapy at baseline were both differentially associated with adherence while remaining ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://eprints.soton.ac.uk/488221/1/s13063-017-1837-3.pdf; Gillespie, David, Farewell, Daniel, Barrett-Lee, Peter, Casbard, Angela, Hawthorne, Anthony Barney, Hurt, Chris, Hurt, Chris, Murray, Nick, Probert, Chris, Stenson, Rachel and Hood, Kerenza (2017) The use of randomisation-based efficacy estimators in non-inferiority trials. Trials, 18 (117). (doi:10.1186/s13063-017-1837-3 ). |
| Availability: |
https://eprints.soton.ac.uk/488221/ |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.E3DF3208 |
| Database: |
BASE |