White, Ian R;
Quartagno, Matteo;
Babiker, Abdel;
Turner, Rebecca;
Parmar, Mahesh;
Walker, Ann;
(2025)
Tackling control risk problems in non-inferiority trials.
BMJ Medicine
, 4
(1)
, Article e000845. 10.1136/bmjmed-2023-000845.
Preview |
Text
Walker_e000845.full.pdf Download (406kB) | Preview |
Abstract
Non-inferiority trials aim to show that major disease related outcomes with a new intervention are not importantly worse than with standard care. These trials are useful when the new intervention has some advantages over standard care (eg, toxicity, convenience, or cost). The ability to show non-inferiority, however, is sensitive to the control risk, the outcome frequency under standard care. Two control risk problems are described that can make non-inferiority trials underpowered or uninterpretable, and two ways of tackling these problems are outlined. Firstly, the choice of effect measure used to express the non-inferiority margin is critical: the effect measure must be based on understanding both the clinical setting and the implications for sample size. Which effect measures can lead to smaller or larger sample sizes is shown. Secondly, investigators need to consider, and potentially plan for, the possibility that the observed control risk might differ from the anticipated risk at the design stage of the trial. How the non-inferiority margin can be adapted in the trial analysis in a statistically principled manner is shown.
| Type: | Article |
|---|---|
| Title: | Tackling control risk problems in non-inferiority trials |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1136/bmjmed-2023-000845 |
| Publisher version: | http://doi.org/10.1136/bmjmed-2023-000845 |
| Language: | English |
| Additional information: | This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/ licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10208922 |
Archive Staff Only
 |
View Item |
